Safety and Efficacy of Empagliflozin (BI 10773) and Sitagliptin Versus Placebo Over 76 Weeks in Patients With Type 2 Diabetes

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01289990
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 2,705
• Locations: 243
• Arms: 13
• Duration (Months): 26.9
• Patients Per Site: 11.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will investigate the efficacy and long term safety and tolerability of BI 10773 in type 2 diabetic patients.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: BI 10773; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: BI 10773; Drug: Placebo; Drug: Placebo; Drug: BI 10773; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: BI 10773; Drug: BI 10773; Drug: BI 10773; Drug: Placebo; Drug: BI 10773; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: Sitagliptin 100mg; Drug: BI 10773; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 2705 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Phase III Double-blind, Extension, Placebo-controlled Parallel Group Safety and Efficacy Trial of BI 10773 (10 and 25mg Once Daily) and Sitagliptin (100mg Once Daily) Given for Minimum 76 Weeks (Incl. 24 Weeks of Preceding Trial) as Monotherapy or With Different Back-ground Therapies in Patients With Type 2 Diabetes Mellitus Previously Completing Trial 1245.19, 1245.20 or 1245.23
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BI 10773 low (drug naive) BI 10773 tablets once daily	Drug: BI 10773; BI 10773 tablets once daily; Drug: Placebo; Placebo matching Sitagliptin; Drug: Placebo; Placebo matching BI 10773 high dose
Experimental: BI 10773 high (drug naive) BI 10773 tablets once daily	Drug: Placebo; Placebo matching Sitagliptin; Drug: BI 10773; BI 10773 tablets once daily; Drug: Placebo; Placebo matching BI 10773 low dose
Placebo Comparator: Placebo (drug naive) Placebo tablets matching BI 10773 / Sitagliptin once daily	Drug: Placebo; Placebo matching BI 10773 low dose; Drug: Placebo; Placebo matching Sitagliptin; Drug: Placebo; Placebo matching BI 10773 high dose
Active Comparator: Sitagliptin 100mg (drug naive) Sitagliptin once daily	Drug: Placebo; Placebo matching BI 10773 high dose; Drug: Placebo; Placebo matching BI 10773 low dose; Drug: Sitagliptin 100mg; Sitagliptin once daily
Experimental: BI 10773 low (pioglitazone) BI 10773 tablets once daily	Drug: BI 10773; BI 10773 tablets once daily; Drug: Placebo; Placebo matching BI 10773 high dose
Experimental: BI 10773 high (pioglitazone) BI 10773 tablets once daily	Drug: BI 10773; BI 10773 tablets once daily; Drug: Placebo; Placebo matching BI 10773 low dose
Placebo Comparator: Placebo (pioglitazone) Placebo tablets matching BI 10773 once daily	Drug: Placebo; Placebo matching BI 10773 low dose; Drug: Placebo; Placebo matching BI 10773 high dose
Experimental: BI 10773 low (metformin) BI 10773 tablets once daily	Drug: Placebo; Placebo matching BI 10773 high dose; Drug: BI 10773; BI 10773 tablets once daily
Experimental: BI 10773 high (metformin) BI 10773 tablets once daily	Drug: BI 10773; BI 10773 tablets once daily; Drug: Placebo; Placebo matching BI 10773 low dose
Placebo Comparator: Placebo (metformin) Placebo tablets matching BI 10773 once daily	Drug: Placebo; Placebo matching BI 10773 low dose; Drug: Placebo; Placebo matching BI 10773 high dose
Experimental: BI 10773 low (metformin+sulfonylurea) BI 10773 tablets once daily	Drug: BI 10773; BI 10773 tablets once daily; Drug: Placebo; Placebo matching BI 10773 high dose
Experimental: BI 10773 high (metformin+sulfonylurea) BI 10773 tablets once daily	Drug: BI 10773; BI 10773 tablets once daily; Drug: Placebo; Placebo matching BI 10773 low dose
Placebo Comparator: Placebo (metformin+sulfonylurea) Placebo tablets matching BI 10773	Drug: Placebo; Placebo matching BI 10773 low dose; Drug: Placebo; Placebo matching BI 10773 high dose

Outcome Measures

Primary Outcome Measures

1. Changes From Baseline in Glycosylated Haemoglobin (HbA1c) (%) After 52 Weeks of Treatment [Baseline and 52 weeks]

   Change from baseline in HbA1c after 52 weeks

2. Changes From Baseline in HbA1c (%) After 76 Weeks of Treatment [Baseline and 76 weeks]

   Change from baseline in HbA1c after 76 weeks

Secondary Outcome Measures

1. HbA1c (%) Changes From Baseline After 76 Weeks of Treatment [Baseline and 76 weeks]

   Change from baseline in HbA1c (%) after 76 weeks using MMRM approach

2. Systolic Blood Pressure: Change From Baseline After 52 Weeks of Treatment [Baseline and 52 weeks]

   Systolic blood pressure - change from baseline after 52 weeks of treatment

3. Systolic Blood Pressure: Change From Baseline After 76 Weeks of Treatment [Baseline and 76 weeks]

   Systolic blood pressure - change from baseline after 76 weeks of treatment

4. Diastolic Blood Pressure: Change From Baseline After 52 Weeks of Treatment [Baseline and 52 weeks]

   Diastolic blood pressure - change from baseline after 52 weeks of treatment

5. Diastolic Blood Pressure: Change From Baseline After 76 Weeks of Treatment [Baseline and 76 weeks]

   Diastolic blood pressure - change from baseline after 76 weeks of treatment

6. Body Weight (kg) Change From Baseline After 52 Weeks of Treatment [Baseline and 52 weeks]

   Body Weight (kg) - Change From Baseline After 52 Weeks of Treatment

7. Body Weight (kg) Change From Baseline After 76 Weeks of Treatment [Baseline and 76 weeks]

   Body Weight (kg) - Change From Baseline After 76 Weeks of Treatment

8. Waist Circumference (cm) Change From Baseline After 52 Weeks of Treatment [Baseline and 52 weeks]

   Waist circumference (cm) - change from baseline after 52 weeks of treatment

9. Waist Circumference (cm) Change From Baseline After 76 Weeks of Treatment [Baseline and 76 weeks]

   Waist circumference (cm) - change from baseline after 76 weeks of treatment

10. Fasting Plasma Glucose Change From Baseline After 52 Weeks of Treatment [Baseline and 52 weeks]

    Fasting plasma glucose - change from baseline after 52 weeks of treatment

11. Fasting Plasma Glucose Change From Baseline After 76 Weeks of Treatment [Baseline and 76 weeks]

    Fasting plasma glucose - change from baseline after 76 weeks of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Patients completing the entire treatment period of the preceding double-blind trial 1245.19, 1245.20 or 1245.23 with or without rescue therapy.

2. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice and local legislation.

Exclusion criteria:

1. Patient who meet one or more of the withdrawal criteria of the treatment period of the previous trial 1245.19, 1245.20 or 1245.23.

2. Indication of liver disease, defined by serum levels of either alanine aminotransferase , aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal as determined during last visit of preceding trial.

3. Impaired renal function defined as glomerular filtration rate<30 ml/min (severe renal impairment, Modification of Diet in Renal Disease formula) as determined during last visit of preceding trial.

4. Contraindications to sitagliptin, pioglitazone, metformin or sulfonylurea according to local label, which started during trial participation in 1245.19, 1245.20 or 1245.23

5. Pre-menopausal women (last menstruation < or = 1 year prior to informed consent) who are nursing or pregnant or are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems, oral, implantable or injectable contraceptives, sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner.

6. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake.

7. Participation in another trial with an investigational drug within 30 days prior to informed consent (except 1245.19, 1245.20 and 1245.23).

8. Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1245.31.10145 Boehringer Ingelheim Investigational Site	Birmingham	Alabama	United States
2	1245.31.10162 Boehringer Ingelheim Investigational Site	Glendale	Arizona	United States
3	1245.31.10124 Boehringer Ingelheim Investigational Site	Mesa	Arizona	United States
4	1245.31.10108 Boehringer Ingelheim Investigational Site	Phoenix	Arizona	United States
5	1245.31.10046 Boehringer Ingelheim Investigational Site	Tempe	Arizona	United States
6	1245.31.10154 Boehringer Ingelheim Investigational Site	Chino	California	United States
7	1245.31.10149 Boehringer Ingelheim Investigational Site	Rancho Cucamonga	California	United States
8	1245.31.10131 Boehringer Ingelheim Investigational Site	West Hills	California	United States
9	1245.31.10038 Boehringer Ingelheim Investigational Site	Northglenn	Colorado	United States
10	1245.31.10127 Boehringer Ingelheim Investigational Site	Waterbury	Connecticut	United States
11	1245.31.10137 Boehringer Ingelheim Investigational Site	Clearwater	Florida	United States
12	1245.31.10133 Boehringer Ingelheim Investigational Site	Jupiter	Florida	United States
13	1245.31.10006 Boehringer Ingelheim Investigational Site	Miami	Florida	United States
14	1245.31.10085 Boehringer Ingelheim Investigational Site	Plantation	Florida	United States
15	1245.31.10080 Boehringer Ingelheim Investigational Site	Decatur	Georgia	United States
16	1245.31.10077 Boehringer Ingelheim Investigational Site	Perry	Georgia	United States
17	1245.31.10001 Boehringer Ingelheim Investigational Site	Chicago	Illinois	United States
18	1245.31.10159 Boehringer Ingelheim Investigational Site	Des Moines	Iowa	United States
19	1245.31.10014 Boehringer Ingelheim Investigational Site	Dubuque	Iowa	United States
20	1245.31.10117 Boehringer Ingelheim Investigational Site	Arkansas City	Kansas	United States
21	1245.31.10157 Boehringer Ingelheim Investigational Site	Newton	Kansas	United States
22	1245.31.10146 Boehringer Ingelheim Investigational Site	Louisville	Kentucky	United States
23	1245.31.10003 Boehringer Ingelheim Investigational Site	Dearborn	Michigan	United States
24	1245.31.10059 Boehringer Ingelheim Investigational Site	New Hyde Park	New York	United States
25	1245.31.10034 Boehringer Ingelheim Investigational Site	Rochester	New York	United States
26	1245.31.10123 Boehringer Ingelheim Investigational Site	Smithtown	New York	United States
27	1245.31.10071 Boehringer Ingelheim Investigational Site	Asheboro	North Carolina	United States
28	1245.31.10086 Boehringer Ingelheim Investigational Site	Salisbury	North Carolina	United States
29	1245.31.10129 Boehringer Ingelheim Investigational Site	Carlisle	Ohio	United States
30	1245.31.10045 Boehringer Ingelheim Investigational Site	Cincinnati	Ohio	United States
31	1245.31.10119 Boehringer Ingelheim Investigational Site	Cincinnati	Ohio	United States
32	1245.31.10130 Boehringer Ingelheim Investigational Site	Gallipolis	Ohio	United States
33	1245.31.10158 Boehringer Ingelheim Investigational Site	Mount Pleasant	South Carolina	United States
34	1245.31.10015 Boehringer Ingelheim Investigational Site	Simpsonville	South Carolina	United States
35	1245.31.10033 Boehringer Ingelheim Investigational Site	Chattanooga	Tennessee	United States
36	1245.31.10112 Boehringer Ingelheim Investigational Site	Memphis	Tennessee	United States
37	1245.31.10156 Boehringer Ingelheim Investigational Site	Houston	Texas	United States
38	1245.31.10151 Boehringer Ingelheim Investigational Site	Hurst	Texas	United States
39	1245.31.10143 Boehringer Ingelheim Investigational Site	Killeen	Texas	United States
40	1245.31.10155 Boehringer Ingelheim Investigational Site	San Antonio	Texas	United States
41	1245.31.32008 Boehringer Ingelheim Investigational Site	Bruxelles		Belgium
42	1245.31.32023 Boehringer Ingelheim Investigational Site	Bruxelles		Belgium
43	1245.31.32003 Boehringer Ingelheim Investigational Site	De Pinte		Belgium
44	1245.31.32015 Boehringer Ingelheim Investigational Site	Deurne		Belgium
45	1245.31.32016 Boehringer Ingelheim Investigational Site	Deurne		Belgium
46	1245.31.32025 Boehringer Ingelheim Investigational Site	Gozée		Belgium
47	1245.31.32019 Boehringer Ingelheim Investigational Site	Leopoldsburg		Belgium
48	1245.31.32024 Boehringer Ingelheim Investigational Site	Linkebeek		Belgium
49	1245.31.32021 Boehringer Ingelheim Investigational Site	Mouscron		Belgium
50	1245.31.32020 Boehringer Ingelheim Investigational Site	Sint-Gillis-Waas		Belgium
51	1245.31.32018 Boehringer Ingelheim Investigational Site	Tielt		Belgium
52	1245.31.32026 Boehringer Ingelheim Investigational Site	Tremelo		Belgium
53	1245.31.20032 Boehringer Ingelheim Investigational Site	Calgary	Alberta	Canada
54	1245.31.20023 Boehringer Ingelheim Investigational Site	Edmonton	Alberta	Canada
55	1245.31.20011 Boehringer Ingelheim Investigational Site	Chilliwack	British Columbia	Canada
56	1245.31.20028 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia	Canada
57	1245.31.20018 Boehringer Ingelheim Investigational Site	Victoria	British Columbia	Canada
58	1245.31.20033 Boehringer Ingelheim Investigational Site	Victoria	British Columbia	Canada
59	1245.31.20015 Boehringer Ingelheim Investigational Site	Winnipeg	Manitoba	Canada
60	1245.31.20012 Boehringer Ingelheim Investigational Site	Moncton	New Brunswick	Canada
61	1245.31.20016 Boehringer Ingelheim Investigational Site	Mount Pearl	Newfoundland and Labrador	Canada
62	1245.31.20024 Boehringer Ingelheim Investigational Site	Paradise	Newfoundland and Labrador	Canada
63	1245.31.20008 Boehringer Ingelheim Investigational Site	St. John's	Newfoundland and Labrador	Canada
64	1245.31.20026 Boehringer Ingelheim Investigational Site	Halifax	Nova Scotia	Canada
65	1245.31.20022 Boehringer Ingelheim Investigational Site	Brampton	Ontario	Canada
66	1245.31.20057 Boehringer Ingelheim Investigational Site	Brampton	Ontario	Canada
67	1245.31.20035 Boehringer Ingelheim Investigational Site	Corunna	Ontario	Canada
68	1245.31.20030 Boehringer Ingelheim Investigational Site	Etobicoke	Ontario	Canada
69	1245.31.20019 Boehringer Ingelheim Investigational Site	Hamilton	Ontario	Canada
70	1245.31.20017 Boehringer Ingelheim Investigational Site	London	Ontario	Canada
71	1245.31.20029 Boehringer Ingelheim Investigational Site	London	Ontario	Canada
72	1245.31.20060 Boehringer Ingelheim Investigational Site	London	Ontario	Canada
73	1245.31.20003 Boehringer Ingelheim Investigational Site	Markham	Ontario	Canada
74	1245.31.20009 Boehringer Ingelheim Investigational Site	Newmarket	Ontario	Canada
75	1245.31.20040 Boehringer Ingelheim Investigational Site	Oakville	Ontario	Canada
76	1245.31.20034 Boehringer Ingelheim Investigational Site	Sarnia	Ontario	Canada
77	1245.31.20005 Boehringer Ingelheim Investigational Site	Strathroy	Ontario	Canada
78	1245.31.20002 Boehringer Ingelheim Investigational Site	Toronto	Ontario	Canada
79	1245.31.20006 Boehringer Ingelheim Investigational Site	Toronto	Ontario	Canada
80	1245.31.20007 Boehringer Ingelheim Investigational Site	Montague	Prince Edward Island	Canada
81	1245.31.20027 Boehringer Ingelheim Investigational Site	Laval	Quebec	Canada
82	1245.31.20025 Boehringer Ingelheim Investigational Site	Montreal	Quebec	Canada
83	1245.31.20036 Boehringer Ingelheim Investigational Site	Sherbrooke	Quebec	Canada
84	1245.31.20058 Boehringer Ingelheim Investigational Site	St-Romuald	Quebec	Canada
85	1245.31.20021 Boehringer Ingelheim Investigational Site	Trois Rivieres	Quebec	Canada
86	1245.31.20038 Boehringer Ingelheim Investigational Site	Ville Saint-Laurent	Quebec	Canada
87	1245.31.20041 Boehringer Ingelheim Investigational Site	Saskatoon	Saskatchewan	Canada
88	1245.31.86007 Boehringer Ingelheim Investigational Site	Beijing		China
89	1245.31.86008 Boehringer Ingelheim Investigational Site	Beijing		China
90	1245.31.86031 Boehringer Ingelheim Investigational Site	Beijing		China
91	1245.31.86032 Boehringer Ingelheim Investigational Site	Beijing		China
92	1245.31.86033 Boehringer Ingelheim Investigational Site	Beijing		China
93	1245.31.86034 Boehringer Ingelheim Investigational Site	Beijing		China
94	1245.31.86035 Boehringer Ingelheim Investigational Site	Beijing		China
95	1245.31.86058 Boehringer Ingelheim Investigational Site	Chongqing		China
96	1245.31.86038 Boehringer Ingelheim Investigational Site	Dalian		China
97	1245.31.86001 Boehringer Ingelheim Investigational Site	Guangzhou		China
98	1245.31.86003 Boehringer Ingelheim Investigational Site	Guangzhou		China
99	1245.31.86052 Boehringer Ingelheim Investigational Site	Guangzhou		China
100	1245.31.86012 Boehringer Ingelheim Investigational Site	Guiyang		China
101	1245.31.86037 Boehringer Ingelheim Investigational Site	Haerbin		China
102	1245.31.86020 Boehringer Ingelheim Investigational Site	Hangzhou		China
103	1245.31.86049 Boehringer Ingelheim Investigational Site	Jinan		China
104	1245.31.86053 Boehringer Ingelheim Investigational Site	Jinan		China
105	1245.31.86018 Boehringer Ingelheim Investigational Site	Jingzhou		China
106	1245.31.86055 Boehringer Ingelheim Investigational Site	Nan Ning		China
107	1245.31.86056 Boehringer Ingelheim Investigational Site	Nan Ning		China
108	1245.31.86019 Boehringer Ingelheim Investigational Site	Nanchang		China
109	1245.31.86042 Boehringer Ingelheim Investigational Site	Nanjing		China
110	1245.31.86043 Boehringer Ingelheim Investigational Site	Nanjing		China
111	1245.31.86016 Boehringer Ingelheim Investigational Site	QingDao		China
112	1245.31.86039 Boehringer Ingelheim Investigational Site	Shanghai		China
113	1245.31.86054 Boehringer Ingelheim Investigational Site	Shantou		China
114	1245.31.86057 Boehringer Ingelheim Investigational Site	Shenyang		China
115	1245.31.86045 Boehringer Ingelheim Investigational Site	Shijiazhuang		China
116	1245.31.86017 Boehringer Ingelheim Investigational Site	Shiyan		China
117	1245.31.86013 Boehringer Ingelheim Investigational Site	Suzhou		China
118	1245.31.86015 Boehringer Ingelheim Investigational Site	Taiyuan		China
119	1245.31.86036 Boehringer Ingelheim Investigational Site	Tianjin		China
120	1245.31.86011 Boehringer Ingelheim Investigational Site	Xi'An		China
121	1245.31.86041 Boehringer Ingelheim Investigational Site	Xi'An		China
122	1245.31.86014 Boehringer Ingelheim Investigational Site	Xiamen		China
123	1245.31.33008 Boehringer Ingelheim Investigational Site	Bersée		France
124	1245.31.33020 Boehringer Ingelheim Investigational Site	Bischheim		France
125	1245.31.33002 Boehringer Ingelheim Investigational Site	Bondy Cedex		France
126	1245.31.33016 Boehringer Ingelheim Investigational Site	Bruay La Buissiere		France
127	1245.31.33001 Boehringer Ingelheim Investigational Site	Corbeil Essonnes		France
128	1245.31.33010 Boehringer Ingelheim Investigational Site	Croix		France
129	1245.31.33009 Boehringer Ingelheim Investigational Site	Hautmont		France
130	1245.31.33003 Boehringer Ingelheim Investigational Site	La Rochelle Cedex 1		France
131	1245.31.33045 Boehringer Ingelheim Investigational Site	Marseille		France
132	1245.31.33004 Boehringer Ingelheim Investigational Site	Narbonne Cedex		France
133	1245.31.33012 Boehringer Ingelheim Investigational Site	Schiltigheim		France
134	1245.31.33013 Boehringer Ingelheim Investigational Site	Strasbourg		France
135	1245.31.33019 Boehringer Ingelheim Investigational Site	Strasbourg		France
136	1245.31.33007 Boehringer Ingelheim Investigational Site	Vieux Condé		France
137	1245.31.33018 Boehringer Ingelheim Investigational Site	Wattrelos		France
138	1245.31.49001 Boehringer Ingelheim Investigational Site	Dormagen		Germany
139	1245.31.49013 Boehringer Ingelheim Investigational Site	Dresden		Germany
140	1245.31.49016 Boehringer Ingelheim Investigational Site	Düsseldorf		Germany
141	1245.31.49009 Boehringer Ingelheim Investigational Site	Flörsheim		Germany
142	1245.31.49015 Boehringer Ingelheim Investigational Site	Frankfurt		Germany
143	1245.31.49019 Boehringer Ingelheim Investigational Site	Haag		Germany
144	1245.31.49004 Boehringer Ingelheim Investigational Site	Hatten		Germany
145	1245.31.49020 Boehringer Ingelheim Investigational Site	Hohenmölsen		Germany
146	1245.31.49007 Boehringer Ingelheim Investigational Site	Künzing		Germany
147	1245.31.49002 Boehringer Ingelheim Investigational Site	Neuwied		Germany
148	1245.31.49008 Boehringer Ingelheim Investigational Site	Nürnberg		Germany
149	1245.31.49010 Boehringer Ingelheim Investigational Site	Rednitzhembach		Germany
150	1245.31.49006 Boehringer Ingelheim Investigational Site	Rehburg-Loccum		Germany
151	1245.31.49011 Boehringer Ingelheim Investigational Site	Rehlingen-Siersburg		Germany
152	1245.31.49005 Boehringer Ingelheim Investigational Site	Saarbrücken		Germany
153	1245.31.49022 Boehringer Ingelheim Investigational Site	Schauenburg		Germany
154	1245.31.49017 Boehringer Ingelheim Investigational Site	St. Ingbert/Oberwürzbach		Germany
155	1245.31.49003 Boehringer Ingelheim Investigational Site	Unterschneidheim		Germany
156	1245.31.30004 Boehringer Ingelheim Investigational Site	Thessaloniki		Greece
157	1245.31.91005 Boehringer Ingelheim Investigational Site	Bangalore		India
158	1245.31.91006 Boehringer Ingelheim Investigational Site	Bangalore		India
159	1245.31.91008 Boehringer Ingelheim Investigational Site	Bangalore		India
160	1245.31.91003 Boehringer Ingelheim Investigational Site	Belgaum		India
161	1245.31.91004 Boehringer Ingelheim Investigational Site	Chennai		India
162	1245.31.91009 Boehringer Ingelheim Investigational Site	Chennai		India
163	1245.31.91001 Boehringer Ingelheim Investigational Site	Coimbatore		India
164	1245.31.91101 Boehringer Ingelheim Investigational Site	Coimbatore		India
165	1245.31.91015 Boehringer Ingelheim Investigational Site	Gulbarga		India
166	1245.31.91104 Boehringer Ingelheim Investigational Site	Indore		India
167	1245.31.91103 Boehringer Ingelheim Investigational Site	Maharashtra		India
168	1245.31.91007 Boehringer Ingelheim Investigational Site	Mumbai, Maharastra		India
169	1245.31.91002 Boehringer Ingelheim Investigational Site	Mumbai		India
170	1245.31.91010 Boehringer Ingelheim Investigational Site	Nagpur		India
171	1245.31.91012 Boehringer Ingelheim Investigational Site	New Delhi		India
172	1245.31.91014 Boehringer Ingelheim Investigational Site	Pune		India
173	1245.31.91105 Boehringer Ingelheim Investigational Site	Pune		India
174	1245.31.35304 Boehringer Ingelheim Investigational Site	Birr, Co. Offaly		Ireland
175	1245.31.35302 Boehringer Ingelheim Investigational Site	Co. Cork		Ireland
176	1245.31.35305 Boehringer Ingelheim Investigational Site	Co. Galway		Ireland
177	1245.31.35303 Boehringer Ingelheim Investigational Site	Co. Wexford		Ireland
178	1245.31.35306 Boehringer Ingelheim Investigational Site	Co. Wexford		Ireland
179	1245.31.81007 Boehringer Ingelheim Investigational Site	Chiyoda-ku, Tokyo		Japan
180	1245.31.81001 Boehringer Ingelheim Investigational Site	Chuo-ku, Tokyo		Japan
181	1245.31.81002 Boehringer Ingelheim Investigational Site	Chuo-ku, Tokyo		Japan
182	1245.31.81005 Boehringer Ingelheim Investigational Site	Ebetsu, Hokkaido		Japan
183	1245.31.81004 Boehringer Ingelheim Investigational Site	Kamakura, Kanagawa		Japan
184	1245.31.81003 Boehringer Ingelheim Investigational Site	Minato-ku, Tokyo		Japan
185	1245.31.81006 Boehringer Ingelheim Investigational Site	Shinjuku-ku, Tokyo		Japan
186	1245.31.81008 Boehringer Ingelheim Investigational Site	Shinjuku-ku, Tokyo		Japan
187	1245.31.81009 Boehringer Ingelheim Investigational Site	Suita, Osaka		Japan
188	1245.31.81010 Boehringer Ingelheim Investigational Site	Ube, Yamaguchi		Japan
189	1245.31.81012 Boehringer Ingelheim Investigational Site	Urasoe, Okinawa		Japan
190	1245.31.81013 Boehringer Ingelheim Investigational Site	Urasoe, Okinawa		Japan
191	1245.31.82012 Boehringer Ingelheim Investigational Site	Anyang		Korea, Republic of
192	1245.31.82011 Boehringer Ingelheim Investigational Site	Goyang		Korea, Republic of
193	1245.31.82009 Boehringer Ingelheim Investigational Site	Ilsan		Korea, Republic of
194	1245.31.82001 Boehringer Ingelheim Investigational Site	Incheon		Korea, Republic of
195	1245.31.82006 Boehringer Ingelheim Investigational Site	Jeonju		Korea, Republic of
196	1245.31.82004 Boehringer Ingelheim Investigational Site	Pusan		Korea, Republic of
197	1245.31.82005 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
198	1245.31.82007 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
199	1245.31.82008 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
200	1245.31.82010 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
201	1245.31.82014 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
202	1245.31.82002 Boehringer Ingelheim Investigational Site	Suwon		Korea, Republic of
203	1245.31.82003 Boehringer Ingelheim Investigational Site	Wonju		Korea, Republic of
204	1245.31.52003 Boehringer Ingelheim Investigational Site	Guadalajara		Mexico
205	1245.31.52004 Boehringer Ingelheim Investigational Site	Guadalajara		Mexico
206	1245.31.52001 Boehringer Ingelheim Investigational Site	Monterrey		Mexico
207	1245.31.52002 Boehringer Ingelheim Investigational Site	Monterrey		Mexico
208	1245.31.63002 Boehringer Ingelheim Investigational Site	Cebu		Philippines
209	1245.31.63003 Boehringer Ingelheim Investigational Site	Davao City		Philippines
210	1245.31.63001 Boehringer Ingelheim Investigational Site	Manila		Philippines
211	1245.31.63004 Boehringer Ingelheim Investigational Site	Manila		Philippines
212	1245.31.63005 Boehringer Ingelheim Investigational Site	Manila		Philippines
213	1245.31.74005 Boehringer Ingelheim Investigational Site	Bratislava		Slovakia
214	1245.31.74002 Boehringer Ingelheim Investigational Site	Lucenec		Slovakia
215	1245.31.74006 Boehringer Ingelheim Investigational Site	Nitra		Slovakia
216	1245.31.74014 Boehringer Ingelheim Investigational Site	Nove Zamky		Slovakia
217	1245.31.74001 Boehringer Ingelheim Investigational Site	Povazska Bystrica		Slovakia
218	1245.31.74004 Boehringer Ingelheim Investigational Site	Presov		Slovakia
219	1245.31.74003 Boehringer Ingelheim Investigational Site	Trebisov		Slovakia
220	1245.31.38003 Boehringer Ingelheim Investigational Site	Celje		Slovenia
221	1245.31.38002 Boehringer Ingelheim Investigational Site	Koper		Slovenia
222	1245.31.38001 Boehringer Ingelheim Investigational Site	Maribor		Slovenia
223	1245.31.41004 Boehringer Ingelheim Investigational Site	Lugano		Switzerland
224	1245.31.41003 Boehringer Ingelheim Investigational Site	Rorschach		Switzerland
225	1245.31.88010 Boehringer Ingelheim Investigational Site	Kaohsiung		Taiwan
226	1245.31.88011 Boehringer Ingelheim Investigational Site	Kaohsiung		Taiwan
227	1245.31.88012 Boehringer Ingelheim Investigational Site	Kaohsiung		Taiwan
228	1245.31.88013 Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan
229	1245.31.88009 Boehringer Ingelheim Investigational Site	Taichung		Taiwan
230	1245.31.88014 Boehringer Ingelheim Investigational Site	Tainan		Taiwan
231	1245.31.88006 Boehringer Ingelheim Investigational Site	Taipei		Taiwan
232	1245.31.88021 Boehringer Ingelheim Investigational Site	Taipei		Taiwan
233	1245.31.88008 Boehringer Ingelheim Investigational Site	Taoyuan County		Taiwan
234	1245.31.90003 Boehringer Ingelheim Investigational Site	Erzurum		Turkey
235	1245.31.90001 Boehringer Ingelheim Investigational Site	Gaziantep		Turkey
236	1245.31.90002 Boehringer Ingelheim Investigational Site	Istanbul		Turkey
237	1245.31.90006 Boehringer Ingelheim Investigational Site	Istanbul		Turkey
238	1245.31.90004 Boehringer Ingelheim Investigational Site	Izmir		Turkey
239	1245.31.75002 Boehringer Ingelheim Investigational Site	Dnepropetrovsk		Ukraine
240	1245.31.75001 Boehringer Ingelheim Investigational Site	Kharkiv		Ukraine
241	1245.31.75006 Boehringer Ingelheim Investigational Site	Lviv		Ukraine
242	1245.31.75004 Boehringer Ingelheim Investigational Site	Vinnitsa		Ukraine
243	1245.31.75003 Boehringer Ingelheim Investigational Site	Vinnytsya		Ukraine

Sponsors and Collaborators

• Boehringer Ingelheim
• Eli Lilly and Company

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01289990
• Other Study ID Numbers: 1245.31; 2010-022718-17
• First Posted: Feb 4, 2011
• Last Update Posted: Jul 15, 2014
• Last Verified: Jul 1, 2014

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Sitagliptin Phosphate; Empagliflozin

Study Results

Participant Flow

Arm/Group Title	Empagliflozin 10 mg (Drug Naive)	Empagliflozin 25 mg (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	Empagliflozin 10 mg (Pioglitazone)	Empagliflozin 25 mg (Pioglitazone)	Placebo (Pioglitazone)	Empagliflozin 10 mg (Metformin)	Empagliflozin 25 mg (Metformin)	Placebo (Metformin)	Empagliflozin 10 mg (Metformin+Sulfonylurea)	Empagliflozin 25 mg (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.20 Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching Empagliflozin 10 mg	Patients rolled over from trial 1245.20 Placebo tablets matching Empagliflozin / Sitagliptin once daily Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Sitagliptin Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching Empagliflozin 25 mg Placebo: Placebo matching Empagliflozin 10 mg Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 Empagliflozin 10 mg tablets once daily Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.19 Empagliflozin 25 mg tablets once daily Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Empagliflozin 10 mg	Patients rolled over from trial 1245.19 Placebo tablets matching Empagliflozin once daily Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.23 Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Empagliflozin 25 mg Empagliflozin 10 mg: Empagliflozin 10 mg once daily	Patients rolled over from trial 1245.23 Empagliflozin 25 mg tablets once daily Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Empagliflozin 10 mg	Patients rolled over from trial 1245.23 Placebo tablets matching Empagliflozin once daily Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.23 Empagliflozin 10 mg tablets once daily Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.23 Empagliflozin 25 mg tablets once daily Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Empagliflozin 10 mg	Patients rolled over from trial 1245.23 Placebo tablets matching Empagliflozin Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Empagliflozin 25 mg
Period Title: Overall Study
STARTED	224	224	228	223	165	168	166	217	214	207	226	218	225
COMPLETED	147	143	119	136	93	94	78	162	139	121	150	150	127
NOT COMPLETED	77	81	109	87	72	74	88	55	75	86	76	68	98

Baseline Characteristics

Arm/Group Title	Empagliflozin 10 mg (Drug Naive)	Empagliflozin 25 mg (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100 mg (Drug Naive)	Empagliflozin 10 mg (Pioglitazone)	Empagliflozin 25 mg (Pioglitazone)	Placebo (Pioglitazone)	Empagliflozin 10 mg (Metformin)	Empagliflozin 25 mg (Metformin)	Placebo (Metformin)	Empagliflozin 10 mg (Metformin+Sulfonylurea)	Empagliflozin 25 mg (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)	Total
Arm/Group Description	Patients rolled over from trial 1245.20 Empagliflozin 10 mg tablets once daily Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.20 Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Sitagliptin Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Empagliflozin 10 mg	Patients rolled over from trial 1245.20 Placebo tablets matching Empagliflozin / Sitagliptin once daily Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Sitagliptin Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching Empagliflozin 25 mg Placebo: Placebo matching Empagliflozin 10 mg Sitagliptin 100 mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 Empagliflozin 10 mg tablets once daily Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.19 Empagliflozin 25 mg tablets once daily Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Empagliflozin 10 mg	Patients rolled over from trial 1245.19 Placebo tablets matching Empagliflozin once daily Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.23 Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Empagliflozin 25 mg Empagliflozin 10 mg: Empagliflozin 10 mg once daily	Patients rolled over from trial 1245.23 Empagliflozin 25 mg tablets once daily Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Empagliflozin 10 mg	Patients rolled over from trial 1245.23 Placebo tablets matching Empagliflozin once daily Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.23 Empagliflozin 10 mg tablets once daily Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Empagliflozin 25 mg	Patients rolled over from trial 1245.23 Empagliflozin 25 mg tablets once daily Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Empagliflozin 10 mg	Patients rolled over from trial 1245.23 Placebo tablets matching Empagliflozin Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Empagliflozin 25 mg	Total of all reporting groups
Overall Participants	224	224	228	223	165	168	165	217	213	207	225	216	225	2700
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.2 (11.6)	53.8 (11.6)	54.9 (10.9)	55.1 (9.9)	54.7 (9.9)	54.2 (8.9)	54.6 (10.5)	55.5 (9.9)	55.6 (10.2)	56.0 (9.7)	57.0 (9.2)	57.4 (9.3)	56.9 (9.2)	55.6 (10.2)
Sex: Female, Male (Count of Participants)
Female	82 36.6%	79 35.3%	105 46.1%	82 36.8%	82 49.7%	83 49.4%	92 55.8%	92 42.4%	93 43.7%	91 44%	112 49.8%	102 47.2%	113 50.2%	1208 44.7%
Male	142 63.4%	145 64.7%	123 53.9%	141 63.2%	83 50.3%	85 50.6%	73 44.2%	125 57.6%	120 56.3%	116 56%	113 50.2%	114 52.8%	112 49.8%	1492 55.3%

Outcome Measures

1. Primary Outcome

Title	Changes From Baseline in Glycosylated Haemoglobin (HbA1c) (%) After 52 Weeks of Treatment
Description	Change from baseline in HbA1c after 52 weeks
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline HbA1c assessment, irrespective of participation in the extension trial. (LOCF:Last observation carried forward)

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	224	224	228	223	165	168	165	217	213	207	225	216	225
Least Squares Mean (Standard Error) [% of HbA1c]	-0.70 (0.05)	-0.82 (0.05)	0.09 (0.05)	-0.58 (0.05)	-0.63 (0.07)	-0.71 (0.07)	-0.03 (0.07)	-0.69 (0.05)	-0.76 (0.05)	-0.07 (0.05)	-0.78 (0.05)	-0.74 (0.05)	-0.04 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments	statistical analysis at week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.79
	Confidence Interval	(2-Sided) 95%; -0.94 to -0.64
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments	statistical analysis at week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.91
	Confidence Interval	(2-Sided) 95%; -1.06 to -0.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments	statistical analysis at week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -0.82 to -0.52
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments	statistical analysis at week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1245
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.27 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments	statistical analysis at week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0022
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -0.39 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -0.79 to -0.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 95%; -0.87 to -0.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.62
	Confidence Interval	(2-Sided) 95%; -0.75 to -0.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.69
	Confidence Interval	(2-Sided) 95%; -0.83 to -0.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.74
	Confidence Interval	(2-Sided) 95%; -0.89 to -0.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.70
	Confidence Interval	(2-Sided) 95%; -0.85 to -0.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

2. Secondary Outcome

Title	HbA1c (%) Changes From Baseline After 76 Weeks of Treatment
Description	Change from baseline in HbA1c (%) after 76 weeks using MMRM approach
Time Frame	Baseline and 76 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline HbA1c assessment, irrespective of participation in the extension trial. (OC: Observed cases)

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	132	132	65	108	71	78	31	130	118	70	110	103	76
Least Squares Mean (Standard Error) [% of HbA1c]	-0.70 (0.07)	-0.77 (0.07)	0.13 (0.08)	-0.48 (0.07)	-0.67 (0.09)	-0.77 (0.08)	-0.05 (0.12)	-0.60 (0.06)	-0.76 (0.07)	0.07 (0.08)	-0.75 (0.08)	-0.75 (0.08)	0.06 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, visit, treatment as fixed effects, and visit by treatment interaction.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.82
	Confidence Interval	(2-Sided) 95%; -1.04 to -0.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, visit, treatment as fixed effects, and visit by treatment interaction.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.90
	Confidence Interval	(2-Sided) 95%; -1.11 to -0.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0322
	Comments	Model includes baseline HbA1c as a covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, visit, treatment as fixed effects, and visit by treatment interaction.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.41 to -0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0038
	Comments	Model includes baseline HbA1c as a covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, visit, treatment as fixed effects, and visit by treatment interaction.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.48 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, visit, treatment as fixed effects, and visit by treatment interaction.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.61
	Confidence Interval	(2-Sided) 95%; -0.83 to -0.40
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, visit, treatment as fixed effects, and visit by treatment interaction.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.62
	Confidence Interval	(2-Sided) 95%; -0.90 to -0.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, visit, treatment as fixed effects, and visit by treatment interaction.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -1.00 to -0.44
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, visit, treatment as fixed effects, and visit by treatment interaction.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -0.87 to -0.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, visit, treatment as fixed effects, and visit by treatment interaction.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.83
	Confidence Interval	(2-Sided) 95%; -1.04 to -0.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, visit, treatment as fixed effects, and visit by treatment interaction.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -1.04 to -0.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, visit, treatment as fixed effects, and visit by treatment interaction.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -1.04 to -0.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

3. Secondary Outcome

Title	Systolic Blood Pressure: Change From Baseline After 52 Weeks of Treatment
Description	Systolic blood pressure - change from baseline after 52 weeks of treatment
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline systolic blood pressure assessment, irrespective of participation in the extension trial. (LOCF)

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	224	224	228	223	165	168	165	217	213	207	225	216	225
Least Squares Mean (Standard Error) [mmHg]	-4.9 (0.8)	-4.5 (0.8)	-1.6 (0.8)	-0.2 (0.8)	-1.8 (0.9)	-3.3 (0.9)	0.6 (0.9)	-3.6 (0.7)	-5.2 (0.7)	-0.7 (0.7)	-3.1 (0.7)	-2.7 (0.7)	-0.2 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-4.6
	Confidence Interval	(2-Sided) 95%; -6.8 to -2.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-4.2
	Confidence Interval	(2-Sided) 95%; -6.4 to -2.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2107
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -3.5 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0033
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-3.3
	Confidence Interval	(2-Sided) 95%; -5.4 to -1.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0105
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.8
	Confidence Interval	(2-Sided) 95%; -5.0 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0543
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -4.9 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.3
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0019
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-3.9
	Confidence Interval	(2-Sided) 95%; -6.4 to -1.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.2
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0045
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-3.0
	Confidence Interval	(2-Sided) 95%; -5.0 to -0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) 95%; -6.6 to -2.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0031
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -4.8 to -1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0096
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -4.4 to -0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0
	Estimation Comments

4. Primary Outcome

Title	Changes From Baseline in HbA1c (%) After 76 Weeks of Treatment
Description	Change from baseline in HbA1c after 76 weeks
Time Frame	Baseline and 76 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline HbA1c assessment, irrespective of participation in the extension trial. (LOCF)

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	224	224	228	223	165	168	165	217	213	207	225	216	225
Least Squares Mean (Standard Deviation) [% of HbA1c]	-0.65 (0.06)	-0.76 (0.06)	0.13 (0.06)	-0.53 (0.06)	-0.61 (0.07)	-0.70 (0.07)	-0.01 (0.07)	-0.62 (0.05)	-0.74 (0.05)	-0.01 (0.05)	-0.74 (0.06)	-0.72 (0.06)	-0.03 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.78
	Confidence Interval	(2-Sided) 95%; -0.94 to -0.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -1.04 to -0.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.66
	Confidence Interval	(2-Sided) 95%; -0.82 to -0.51
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1310
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.28 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0050
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.38 to -0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95%; -0.79 to -0.40
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.69
	Confidence Interval	(2-Sided) 95%; -0.88 to -0.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.61
	Confidence Interval	(2-Sided) 95%; -0.75 to -0.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.73
	Confidence Interval	(2-Sided) 95%; -0.88 to -0.58
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -0.87 to -0.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline HbA1c as a linear covariate, baseline estimated glomerular filtration rate (eGFR), geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.69
	Confidence Interval	(2-Sided) 95%; -0.85 to -0.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

5. Secondary Outcome

Title	Systolic Blood Pressure: Change From Baseline After 76 Weeks of Treatment
Description	Systolic blood pressure - change from baseline after 76 weeks of treatment
Time Frame	Baseline and 76 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline systolic blood pressure assessment, irrespective of participation in the extension trial -LOCF

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	224	224	228	223	165	168	165	217	213	207	225	216	225
Least Squares Mean (Standard Error) [mmHg]	-4.1 (0.8)	-4.2 (0.8)	-0.7 (0.8)	-0.3 (0.8)	-1.7 (0.9)	-3.4 (0.9)	0.3 (0.9)	-5.2 (0.8)	-4.5 (0.8)	-0.8 (0.8)	-3.8 (0.7)	-3.7 (0.7)	-1.6 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 95%; -5.5 to -1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 95%; -5.6 to -1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7241
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -1.8 to 2.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -5.9 to -1.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-3.8
	Confidence Interval	(2-Sided) 95%; -6.0 to -1.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0987
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -4.5 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.2
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0028
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -6.1 to -1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.2
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95%; -6.6 to -2.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -5.9 to -1.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0213
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -4.1 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0288
	Comments	Model includes baseline sys blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -4.1 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0
	Estimation Comments

6. Secondary Outcome

Title	Diastolic Blood Pressure: Change From Baseline After 52 Weeks of Treatment
Description	Diastolic blood pressure - change from baseline after 52 weeks of treatment
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline diastolic blood pressure assessment, irrespective of participation in the extension trial -LOCF

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	224	224	228	223	165	168	165	217	213	207	225	216	225
Least Squares Mean (Standard Error) [mmHg]	-1.3 (0.5)	-1.9 (0.5)	-0.2 (0.5)	-0.3 (0.5)	-1.6 (0.5)	-2.2 (0.5)	0.4 (0.5)	-2.2 (0.5)	-2.1 (0.5)	-0.4 (0.5)	-1.7 (0.5)	-1.6 (0.5)	-1.0 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1058
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -2.4 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0109
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -3.1 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8259
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.5 to 1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1660
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -2.3 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0212
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.9 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0076
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -3.4 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -4.1 to -1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0170
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -3.2 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0236
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -3.1 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2523
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -2.0 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3494
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6
	Estimation Comments

7. Secondary Outcome

Title	Diastolic Blood Pressure: Change From Baseline After 76 Weeks of Treatment
Description	Diastolic blood pressure - change from baseline after 76 weeks of treatment
Time Frame	Baseline and 76 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline diastolic blood pressure assessment, irrespective of participation in the extension trial -LOCF

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	224	224	228	223	165	168	165	217	213	207	225	216	225
Least Squares Mean (Standard Error) [mmHg]	-1.6 (0.5)	-1.6 (0.5)	-0.6 (0.5)	-0.1 (0.5)	-1.3 (0.5)	-2.0 (0.5)	0.2 (0.5)	-2.5 (0.5)	-1.9 (0.5)	-0.5 (0.5)	-2.6 (0.5)	-2.3 (0.5)	-1.4 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1568
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -2.3 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1323
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -2.4 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4327
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0289
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.8 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0231
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.9 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0513
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -3.0 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.8
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0038
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -3.7 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.8
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0084
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -3.4 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0677
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -2.8 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0814
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -2.4 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1785
	Comments	Model includes baseline diastolic blood pressure, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -2.2 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

8. Secondary Outcome

Title	Body Weight (kg) Change From Baseline After 52 Weeks of Treatment
Description	Body Weight (kg) - Change From Baseline After 52 Weeks of Treatment
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline body weight assessment, irrespective of participation in the extension trial. - LOCF

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	224	224	228	223	165	168	165	217	213	207	225	216	225
Least Squares Mean (Standard Error) [kg]	-2.70 (0.19)	-2.61 (0.19)	-0.48 (0.19)	0.14 (0.19)	-1.50 (0.24)	-1.40 (0.24)	0.59 (0.24)	-2.27 (0.19)	-2.84 (0.19)	-0.54 (0.20)	-2.28 (0.18)	-2.32 (0.19)	-0.31 (0.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.22
	Confidence Interval	(2-Sided) 95%; -2.75 to -1.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.14
	Confidence Interval	(2-Sided) 95%; -2.66 to -1.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0223
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.09 to 1.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.84
	Confidence Interval	(2-Sided) 95%; -3.37 to -2.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.75
	Confidence Interval	(2-Sided) 95%; -3.28 to -2.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.09
	Confidence Interval	(2-Sided) 95%; -2.76 to -1.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.99
	Confidence Interval	(2-Sided) 95%; -2.66 to -1.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.73
	Confidence Interval	(2-Sided) 95%; -2.27 to -1.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.30
	Confidence Interval	(2-Sided) 95%; -2.85 to -1.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.97
	Confidence Interval	(2-Sided) 95%; -2.48 to -1.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.01
	Confidence Interval	(2-Sided) 95%; -2.52 to -1.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments

9. Secondary Outcome

Title	Body Weight (kg) Change From Baseline After 76 Weeks of Treatment
Description	Body Weight (kg) - Change From Baseline After 76 Weeks of Treatment
Time Frame	Baseline and 76 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline body weight assessment, irrespective of participation in the extension trial -LOCF

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	224	224	228	223	165	168	165	217	213	207	225	216	225
Least Squares Mean (Standard Error) [kg]	-2.24 (0.20)	-2.45 (0.20)	-0.43 (0.20)	0.10 (0.20)	-1.47 (0.26)	-1.21 (0.26)	0.50 (0.26)	-2.39 (0.21)	-2.65 (0.22)	-0.46 (0.22)	-2.44 (0.19)	-2.28 (0.20)	-0.63 (0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.81
	Confidence Interval	(2-Sided) 95%; -2.35 to -1.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.02
	Confidence Interval	(2-Sided) 95%; -2.56 to -1.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0546
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; -0.01 to 1.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.34
	Confidence Interval	(2-Sided) 95%; -2.89 to -1.80
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.56
	Confidence Interval	(2-Sided) 95%; -3.10 to -2.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.97
	Confidence Interval	(2-Sided) 95%; -2.69 to -1.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.37
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.71
	Confidence Interval	(2-Sided) 95%; -2.43 to -0.99
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.37
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.93
	Confidence Interval	(2-Sided) 95%; -2.52 to -1.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.30
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.19
	Confidence Interval	(2-Sided) 95%; -2.79 to -1.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.30
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.81
	Confidence Interval	(2-Sided) 95%; -2.34 to -1.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline weight, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.64
	Confidence Interval	(2-Sided) 95%; -2.18 to -1.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

10. Secondary Outcome

Title	Waist Circumference (cm) Change From Baseline After 52 Weeks of Treatment
Description	Waist circumference (cm) - change from baseline after 52 weeks of treatment
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline waist circumference assessment, irrespective of participation in the extension trial -LOCF

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	223	224	228	221	163	167	165	216	213	207	222	215	219
Least Squares Mean (Standard Error) [cm]	-2.0 (0.4)	-1.7 (0.4)	0.1 (0.4)	0.4 (0.4)	-1.5 (0.4)	-1.1 (0.4)	-0.1 (0.4)	-1.5 (0.3)	-2.0 (0.3)	-0.4 (0.3)	-1.5 (0.3)	-1.5 (0.3)	-0.2 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -3.1 to -1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -2.8 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5052
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -3.5 to -1.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -3.1 to -1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0064
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.6 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0642
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -2.1 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0053
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.8 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.3 to -0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.1 to -0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.1 to -0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

11. Secondary Outcome

Title	Waist Circumference (cm) Change From Baseline After 76 Weeks of Treatment
Description	Waist circumference (cm) - change from baseline after 76 weeks of treatment
Time Frame	Baseline and 76 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline waist circumference assessment, irrespective of participation in the extension trial -LOCF

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	223	224	228	221	163	167	165	216	213	207	222	215	219
Least Squares Mean (Standard Error) [cm]	-1.5 (0.4)	-1.6 (0.4)	0.1 (0.4)	0.5 (0.4)	-1.4 (0.4)	-0.9 (0.4)	0.0 (0.4)	-1.8 (0.3)	-1.3 (0.3)	-0.2 (0.3)	-1.6 (0.3)	-1.4 (0.3)	-0.3 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0028
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.7 to -0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0019
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -2.8 to -0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5044
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -3.1 to -0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -3.2 to -1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0109
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -2.5 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1238
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.4 to -0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0076
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -1.9 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0049
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.1 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0178
	Comments	Model includes baseline waist circumference, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.9 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

12. Secondary Outcome

Title	Fasting Plasma Glucose Change From Baseline After 52 Weeks of Treatment
Description	Fasting plasma glucose - change from baseline after 52 weeks of treatment
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline fasting plasma glucose assessment, irrespective of participation in the extension trial -LOCF

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	223	223	226	223	163	168	165	216	213	207	225	215	224
Least Squares Mean (Standard Error) [mg/dL]	-18.9 (2.0)	-23.9 (2.0)	13.3 (2.0)	-3.9 (2.0)	-16.7 (2.8)	-20.7 (2.8)	10.3 (2.8)	-16.7 (1.9)	-19.7 (1.9)	7.6 (2.0)	-18.4 (2.1)	-19.3 (2.1)	9.4 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-32.3
	Confidence Interval	(2-Sided) 95%; -37.8 to -26.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-37.2
	Confidence Interval	(2-Sided) 95%; -42.8 to -31.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-17.3
	Confidence Interval	(2-Sided) 95%; -22.9 to -11.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-15.0
	Confidence Interval	(2-Sided) 95%; -20.6 to -9.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-19.9
	Confidence Interval	(2-Sided) 95%; -25.5 to -14.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-27.1
	Confidence Interval	(2-Sided) 95%; -35.0 to -19.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.0
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-31.0
	Confidence Interval	(2-Sided) 95%; -38.9 to -23.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.0
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-24.3
	Confidence Interval	(2-Sided) 95%; -29.7 to -18.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.7
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-27.3
	Confidence Interval	(2-Sided) 95%; -32.7 to -21.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-27.8
	Confidence Interval	(2-Sided) 95%; -33.6 to -22.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-28.7
	Confidence Interval	(2-Sided) 95%; -34.5 to -22.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0
	Estimation Comments

13. Secondary Outcome

Title	Fasting Plasma Glucose Change From Baseline After 76 Weeks of Treatment
Description	Fasting plasma glucose - change from baseline after 76 weeks of treatment
Time Frame	Baseline and 76 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) which contained all randomised patients who received at least 1 dose of study drug and had a baseline fasting plasma glucose assessment, irrespective of participation in the extension trial -LOCF

Arm/Group Title	BI 10773 Low (Drug Naive)	BI 10773 High (Drug Naive)	Placebo (Drug Naive)	Sitagliptin 100mg (Drug Naive)	BI 10773 Low (Pioglitazone)	BI 10773 High (Pioglitazone)	Placebo (Pioglitazone)	BI 10773 Low (Metformin)	BI 10773 High (Metformin)	Placebo (Metformin)	BI 10773 Low (Metformin+Sulfonylurea)	BI 10773 High (Metformin+Sulfonylurea)	Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 BI 10773 tablets once daily Placebo: Placebo matching Sitagliptin BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.20 Placebo tablets matching BI 10773 / Sitagliptin once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching Sitagliptin Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching BI 10773 high dose Placebo: Placebo matching BI 10773 low dose Sitagliptin 100mg: Sitagliptin once daily	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.19 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.19 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose BI 10773: BI 10773 tablets once daily	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 once daily Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 high dose	Patients rolled over from trial 1245.23 BI 10773 tablets once daily BI 10773: BI 10773 tablets once daily Placebo: Placebo matching BI 10773 low dose	Patients rolled over from trial 1245.23 Placebo tablets matching BI 10773 Placebo: Placebo matching BI 10773 low dose Placebo: Placebo matching BI 10773 high dose
Measure Participants	223	223	226	223	163	168	165	216	213	207	225	215	224
Least Squares Mean (Standard Error) [mg/dL]	-17.2 (2.1)	-20.4 (2.1)	14.4 (2.1)	-1.8 (2.1)	-13.9 (2.9)	-18.0 (2.9)	9.4 (2.9)	-14.5 (2.0)	-20.9 (2.0)	10.5 (2.0)	-19.5 (2.2)	-20.4 (2.2)	11.4 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-31.7
	Confidence Interval	(2-Sided) 95%; -37.4 to -25.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Placebo (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-34.9
	Confidence Interval	(2-Sided) 95%; -40.7 to -29.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-16.3
	Confidence Interval	(2-Sided) 95%; -22.1 to -10.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-15.4
	Confidence Interval	(2-Sided) 95%; -21.2 to -9.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Drug Naive), Sitagliptin 100mg (Drug Naive)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-18.7
	Confidence Interval	(2-Sided) 95%; -24.5 to -12.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.0
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-23.3
	Confidence Interval	(2-Sided) 95%; -31.4 to -15.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.1
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Pioglitazone), Placebo (Pioglitazone)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-27.4
	Confidence Interval	(2-Sided) 95%; -35.4 to -19.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.1
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-25.1
	Confidence Interval	(2-Sided) 95%; -30.5 to -19.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin), Placebo (Metformin)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-31.4
	Confidence Interval	(2-Sided) 95%; -36.9 to -25.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	BI 10773 Low (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-31.0
	Confidence Interval	(2-Sided) 95%; -37.0 to -24.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	BI 10773 High (Metformin+Sulfonylurea), Placebo (Metformin+Sulfonylurea)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Model includes baseline fasting plasma glucose, baseline HbA1c as covariates, baseline eGFR, geographic region, and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-31.8
	Confidence Interval	(2-Sided) 95%; -37.9 to -25.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1
	Estimation Comments

Adverse Events

Time Frame	From signing of the informed consent until 7 days (inclusive) after last treatment
Adverse Event Reporting Description	For all safety analyses (except drug-related AEs), patients are assigned to the treatment group "as treated" at inclusion (if a patient erroneously receives the wrong trial drug, the patient is analysed as per the first treatment received). For drug-related AEs, patients are assigned to the actual treatment at onset of AE.
Arm/Group Title	Empagliflozin 10 mg (Drug Naive)		Empagliflozin 25 mg (Drug Naive)		Placebo (Drug Naive)		Sitagliptin 100mg (Drug Naive)		Empagliflozin 10 mg (Pioglitazone)		Empagliflozin 25 mg (Pioglitazone)		Placebo (Pioglitazone)		Empagliflozin 10 mg (Metformin)		Empagliflozin 25 mg (Metformin)		Placebo (Metformin)		Empagliflozin 10 mg (Metformin+Sulfonylurea)		Empagliflozin 25 mg (Metformin+Sulfonylurea)		Placebo (Metformin+Sulfonylurea)
Arm/Group Description	Patients rolled over from trial 1245.20 Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching Empagliflozin 25 mg		Patients rolled over from trial 1245.20 Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Sitagliptin Placebo: Placebo matching Empagliflozin 10 mg		Patients rolled over from trial 1245.20 Placebo tablets matching Empagliflozin / Sitagliptin once daily Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Sitagliptin Placebo: Placebo matching Empagliflozin 25 mg		Patients rolled over from trial 1245.20 Sitagliptin once daily Placebo: Placebo matching Empagliflozin 25 mg Placebo: Placebo matching Empagliflozin 10 mg Sitagliptin 100mg: Sitagliptin once daily		Patients rolled over from trial 1245.19 Empagliflozin 10 mg tablets once daily Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Empagliflozin 25 mg		Patients rolled over from trial 1245.19 Empagliflozin 25 mg tablets once daily Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Empagliflozin 10 mg		Patients rolled over from trial 1245.19 Placebo tablets matching Empagliflozin once daily Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Empagliflozin 25 mg		Patients rolled over from trial 1245.23 Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Empagliflozin 25 mg Empagliflozin 10 mg: Empagliflozin 10 mg once daily		Patients rolled over from trial 1245.23 Empagliflozin 25 mg tablets once daily Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Empagliflozin 10 mg		Patients rolled over from trial 1245.23 Placebo tablets matching Empagliflozin once daily Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Empagliflozin 25 mg		Patients rolled over from trial 1245.23 Empagliflozin 10 mg tablets once daily Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily Placebo: Placebo matching Empagliflozin 25 mg		Patients rolled over from trial 1245.23 Empagliflozin 25 mg tablets once daily Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily Placebo: Placebo matching Empagliflozin 10 mg		Patients rolled over from 1245.23 Placebo tablets matching Empagliflozin Placebo: Placebo matching Empagliflozin 10 mg Placebo: Placebo matching Empagliflozin 25 mg
All Cause Mortality
	Empagliflozin 10 mg (Drug Naive)		Empagliflozin 25 mg (Drug Naive)		Placebo (Drug Naive)		Sitagliptin 100mg (Drug Naive)		Empagliflozin 10 mg (Pioglitazone)		Empagliflozin 25 mg (Pioglitazone)		Placebo (Pioglitazone)		Empagliflozin 10 mg (Metformin)		Empagliflozin 25 mg (Metformin)		Placebo (Metformin)		Empagliflozin 10 mg (Metformin+Sulfonylurea)		Empagliflozin 25 mg (Metformin+Sulfonylurea)		Placebo (Metformin+Sulfonylurea)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Empagliflozin 10 mg (Drug Naive)		Empagliflozin 25 mg (Drug Naive)		Placebo (Drug Naive)		Sitagliptin 100mg (Drug Naive)		Empagliflozin 10 mg (Pioglitazone)		Empagliflozin 25 mg (Pioglitazone)		Placebo (Pioglitazone)		Empagliflozin 10 mg (Metformin)		Empagliflozin 25 mg (Metformin)		Placebo (Metformin)		Empagliflozin 10 mg (Metformin+Sulfonylurea)		Empagliflozin 25 mg (Metformin+Sulfonylurea)		Placebo (Metformin+Sulfonylurea)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/229 (10%)		25/224 (11.2%)		16/223 (7.2%)		18/223 (8.1%)		11/165 (6.7%)		13/165 (7.9%)		15/168 (8.9%)		24/206 (11.7%)		19/217 (8.8%)		17/214 (7.9%)		31/225 (13.8%)		29/224 (12.9%)		24/217 (11.1%)
Blood and lymphatic system disorders
Normochromic normocytic anaemia	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Febrile neutropenia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Pancytopenia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Cardiac disorders
Coronary artery disease	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		2/206 (1%)		2/217 (0.9%)		1/214 (0.5%)		0/225 (0%)		1/224 (0.4%)		1/217 (0.5%)
Acute myocardial infarction	1/229 (0.4%)		0/224 (0%)		2/223 (0.9%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Angina pectoris	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		2/225 (0.9%)		0/224 (0%)		1/217 (0.5%)
Arteriosclerosis coronary artery	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		2/217 (0.9%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Acute coronary syndrome	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Angina unstable	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Atrial fibrillation	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Atrial flutter	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Cardio-respiratory arrest	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Myocardial ischaemia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		1/168 (0.6%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Cardiac failure	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Cardiac failure congestive	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Congestive cardiomyopathy	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Myocardial infarction	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		1/214 (0.5%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Prinzmetal angina	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Aortic valve stenosis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Stress cardiomyopathy	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Ventricular tachycardia	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Cardiogenic shock	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Left ventricular failure	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Acute left ventricular failure	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Congenital, familial and genetic disorders
Gilbert's syndrome	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Hydrocele	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Phimosis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Syringomyelia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Ear and labyrinth disorders
Vertigo positional	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Sudden hearing loss	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Tinnitus	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Vertigo	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Meniere's disease	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Endocrine disorders
Empty sella syndrome	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Goitre	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Hyperparathyroidism	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Eye disorders
Diabetic retinopathy	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Cataract	1/229 (0.4%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Dacryostenosis acquired	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Glaucoma	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Lens dislocation	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Retinal detachment	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Retinal vein occlusion	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Vitreous haemorrhage	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Gastrointestinal disorders
Gastritis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		2/224 (0.9%)		0/217 (0%)
Haemorrhoids	2/229 (0.9%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Anal fissure	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Constipation	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Oesophageal rupture	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Gastric polyps	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Gastric ulcer	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Gastrooesophageal reflux disease	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Inguinal hernia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		1/217 (0.5%)
Nausea	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Vomiting	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Abdominal hernia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Abdominal pain	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Colitis ulcerative	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Duodenal ulcer	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Faecaloma	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Gastrointestinal haemorrhage	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Intestinal obstruction	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Large intestine polyp	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
General disorders
Chest pain	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		1/217 (0.5%)
Death	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Chest discomfort	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Non-cardiac chest pain	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Hernia	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Impaired healing	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Sudden death	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Hepatobiliary disorders
Cholecystitis	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Cholecystitis acute	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Liver injury	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Hepatitis toxic	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Cholelithiasis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Cirrhosis alcoholic	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Drug-induced liver injury	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Liver disorder	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Jaundice	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Immune system disorders
Hypersensitivity	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Infections and infestations
Cellulitis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		2/165 (1.2%)		1/168 (0.6%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Gastroenteritis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		2/214 (0.9%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Pneumonia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		2/224 (0.9%)		0/217 (0%)
Urinary tract infection	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		2/225 (0.9%)		0/224 (0%)		0/217 (0%)
Amoebic colitis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Cervicitis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Dengue fever	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Pseudomonas infection	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Pyelonephritis acute	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Septic shock	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Urosepsis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Anal abscess	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Appendicitis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Gangrene	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Herpes zoster	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Sepsis	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Subcutaneous abscess	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Atypical pneumonia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Cytomegalovirus infection	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Genital infection	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Herpes virus infection	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Infected skin ulcer	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Infective exacerbation of chronic obstructive airways disease	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Listeria sepsis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Peritonitis	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Pulmonary tuberculosis	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Salmonellosis	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Schistosomiasis	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Upper respiratory tract infection	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Comminuted fracture	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Fall	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		1/206 (0.5%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Hand fracture	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Humerus fracture	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Injury	1/229 (0.4%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Joint dislocation	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Road traffic accident	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Traumatic fracture	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Upper limb fracture	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Facial bones fracture	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Femur fracture	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Hip fracture	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Ligament rupture	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Tendon rupture	1/229 (0.4%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Tibia fracture	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Animal bite	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Femoral neck fracture	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Ligament sprain	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Meniscus injury	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Multiple fractures	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Muscle strain	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Neck injury	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Post-traumatic neck syndrome	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Subdural haematoma	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Investigations
Haemoglobin decreased	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Blood creatine phosphokinase increased	1/229 (0.4%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Blood creatinine increased	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Smear cervix abnormal	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Metabolism and nutrition disorders
Dehydration	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Lactic acidosis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Diabetes mellitus inadequate control	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Diabetic ketoacidosis	1/229 (0.4%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Hyperglycaemia	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Hyperlipidaemia	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Hyponatraemia	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Insulin-requiring type 2 diabetes mellitus	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	2/229 (0.9%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		2/206 (1%)		1/217 (0.5%)		1/214 (0.5%)		1/225 (0.4%)		0/224 (0%)		2/217 (0.9%)
Spondylolisthesis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		2/225 (0.9%)		0/224 (0%)		0/217 (0%)
Arthralgia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Back pain	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Joint swelling	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Musculoskeletal chest pain	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Osteoarthropathy	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Periarthritis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Foot deformity	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Intervertebral disc protrusion	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		1/224 (0.4%)		1/217 (0.5%)
Lumbar spinal stenosis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		1/224 (0.4%)		1/217 (0.5%)
Musculoskeletal pain	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Rotator cuff syndrome	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Spinal osteoarthritis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Femoroacetabular impingement	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Intervertebral disc disorder	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Plica syndrome	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Synovitis	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Tenosynovitis stenosans	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Facet joint syndrome	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Pancreatic carcinoma	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Basal cell carcinoma	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Colon cancer metastatic	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Gastric cancer	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Malignant melanoma	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Non-small cell lung cancer	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Ovarian neoplasm	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Prostate cancer	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Prostatic adenoma	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Rectosigmoid cancer	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Squamous cell carcinoma of lung	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Adenocarcinoma	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Anaplastic large cell lymphoma T- and null-cell types	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Bile duct cancer	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Breast cancer female	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Cholangiocarcinoma	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Colon cancer	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Gastrooesophageal cancer	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Lung neoplasm malignant	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Metastases to bone	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Metastases to central nervous system	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Parathyroid tumour benign	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Tongue neoplasm malignant stage unspecified	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Adenocarcinoma of colon	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Renal cell carcinoma	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Laryngeal cancer	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Nervous system disorders
Cerebral infarction	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		2/214 (0.9%)		1/225 (0.4%)		1/224 (0.4%)		1/217 (0.5%)
Cerebrovascular accident	0/229 (0%)		2/224 (0.9%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Brain stem infarction	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Carotid artery stenosis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Presyncope	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Brain stem stroke	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Carotid artery disease	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Cerebral ischaemia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Diabetic neuropathy	1/229 (0.4%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		1/217 (0.5%)
Dizziness	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		1/217 (0.5%)
Lacunar infarction	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Radiculitis brachial	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Syncope	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Transient ischaemic attack	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Trigeminal neuralgia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Carpal tunnel syndrome	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Cervicobrachial syndrome	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Convulsion	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Intercostal neuralgia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Ischaemic stroke	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Sciatica	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Subarachnoid haemorrhage	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Vascular headache	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Vertebrobasilar insufficiency	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Psychiatric disorders
Stress	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Renal and urinary disorders
Nephrolithiasis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		2/206 (1%)		0/217 (0%)		0/214 (0%)		2/225 (0.9%)		1/224 (0.4%)		0/217 (0%)
Renal failure acute	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		2/214 (0.9%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Diabetic nephropathy	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Renal tubular necrosis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Cystitis haemorrhagic	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Dysuria	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Hypotonic urinary bladder	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Polyuria	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Renal failure	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Reproductive system and breast disorders
Endometrial hyperplasia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		1/165 (0.6%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Benign prostatic hyperplasia	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Postmenopausal haemorrhage	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Breast mass	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Menorrhagia	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome	0/229 (0%)		0/224 (0%)		1/223 (0.4%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Asthma	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Chronic obstructive pulmonary disease	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Haemothorax	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Hypercapnia	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Pleurisy	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Pneumothorax	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		1/225 (0.4%)		0/224 (0%)		0/217 (0%)
Upper airway resistance syndrome	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Pleural effusion	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Pulmonary oedema	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Respiratory failure	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Skin and subcutaneous tissue disorders
Diabetic foot	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Skin ulcer	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		1/165 (0.6%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Surgical and medical procedures
Knee arthroplasty	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Hip arthroplasty	0/229 (0%)		1/224 (0.4%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Photocoagulation	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Vitrectomy	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Leg amputation	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Vascular disorders
Peripheral arterial occlusive disease	0/229 (0%)		0/224 (0%)		0/223 (0%)		1/223 (0.4%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		1/214 (0.5%)		0/225 (0%)		2/224 (0.9%)		0/217 (0%)
Femoral artery occlusion	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Haematoma	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Vascular calcification	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Vascular occlusion	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		1/168 (0.6%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Deep vein thrombosis	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		1/217 (0.5%)
Hypertension	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		1/217 (0.5%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Ischaemia	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		1/206 (0.5%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Arterial occlusive disease	0/229 (0%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		1/224 (0.4%)		0/217 (0%)
Venous occlusion	1/229 (0.4%)		0/224 (0%)		0/223 (0%)		0/223 (0%)		0/165 (0%)		0/165 (0%)		0/168 (0%)		0/206 (0%)		0/217 (0%)		0/214 (0%)		0/225 (0%)		0/224 (0%)		0/217 (0%)
Other (Not Including Serious) Adverse Events
	Empagliflozin 10 mg (Drug Naive)		Empagliflozin 25 mg (Drug Naive)		Placebo (Drug Naive)		Sitagliptin 100mg (Drug Naive)		Empagliflozin 10 mg (Pioglitazone)		Empagliflozin 25 mg (Pioglitazone)		Placebo (Pioglitazone)		Empagliflozin 10 mg (Metformin)		Empagliflozin 25 mg (Metformin)		Placebo (Metformin)		Empagliflozin 10 mg (Metformin+Sulfonylurea)		Empagliflozin 25 mg (Metformin+Sulfonylurea)		Placebo (Metformin+Sulfonylurea)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/229 (58.5%)		110/224 (49.1%)		92/223 (41.3%)		116/223 (52%)		110/165 (66.7%)		96/165 (58.2%)		107/168 (63.7%)		122/206 (59.2%)		113/217 (52.1%)		106/214 (49.5%)		146/225 (64.9%)		147/224 (65.6%)		142/217 (65.4%)
Blood and lymphatic system disorders
Anaemia	8/229 (3.5%)		2/224 (0.9%)		2/223 (0.9%)		0/223 (0%)		13/165 (7.9%)		7/165 (4.2%)		11/168 (6.5%)		5/206 (2.4%)		2/217 (0.9%)		3/214 (1.4%)		5/225 (2.2%)		1/224 (0.4%)		4/217 (1.8%)
Gastrointestinal disorders
Dyspepsia	2/229 (0.9%)		1/224 (0.4%)		2/223 (0.9%)		2/223 (0.9%)		2/165 (1.2%)		10/165 (6.1%)		4/168 (2.4%)		2/206 (1%)		3/217 (1.4%)		2/214 (0.9%)		4/225 (1.8%)		3/224 (1.3%)		4/217 (1.8%)
Diarrhoea	9/229 (3.9%)		12/224 (5.4%)		6/223 (2.7%)		8/223 (3.6%)		5/165 (3%)		6/165 (3.6%)		4/168 (2.4%)		10/206 (4.9%)		10/217 (4.6%)		9/214 (4.2%)		7/225 (3.1%)		10/224 (4.5%)		7/217 (3.2%)
Infections and infestations
Urinary tract infection	21/229 (9.2%)		20/224 (8.9%)		13/223 (5.8%)		18/223 (8.1%)		33/165 (20%)		29/165 (17.6%)		33/168 (19.6%)		23/206 (11.2%)		25/217 (11.5%)		18/214 (8.4%)		28/225 (12.4%)		33/224 (14.7%)		33/217 (15.2%)
Nasopharyngitis	27/229 (11.8%)		32/224 (14.3%)		25/223 (11.2%)		27/223 (12.1%)		7/165 (4.2%)		10/165 (6.1%)		9/168 (5.4%)		39/206 (18.9%)		36/217 (16.6%)		29/214 (13.6%)		24/225 (10.7%)		36/224 (16.1%)		34/217 (15.7%)
Upper respiratory tract infection	12/229 (5.2%)		17/224 (7.6%)		16/223 (7.2%)		19/223 (8.5%)		11/165 (6.7%)		9/165 (5.5%)		15/168 (8.9%)		17/206 (8.3%)		7/217 (3.2%)		21/214 (9.8%)		24/225 (10.7%)		18/224 (8%)		21/217 (9.7%)
Bronchitis	10/229 (4.4%)		11/224 (4.9%)		6/223 (2.7%)		12/223 (5.4%)		2/165 (1.2%)		5/165 (3%)		4/168 (2.4%)		8/206 (3.9%)		6/217 (2.8%)		6/214 (2.8%)		8/225 (3.6%)		12/224 (5.4%)		8/217 (3.7%)
Influenza	9/229 (3.9%)		6/224 (2.7%)		6/223 (2.7%)		6/223 (2.7%)		4/165 (2.4%)		0/165 (0%)		4/168 (2.4%)		5/206 (2.4%)		4/217 (1.8%)		6/214 (2.8%)		4/225 (1.8%)		7/224 (3.1%)		11/217 (5.1%)
Investigations
Glycosylated haemoglobin increased	9/229 (3.9%)		10/224 (4.5%)		1/223 (0.4%)		6/223 (2.7%)		8/165 (4.8%)		3/165 (1.8%)		2/168 (1.2%)		9/206 (4.4%)		6/217 (2.8%)		2/214 (0.9%)		12/225 (5.3%)		6/224 (2.7%)		11/217 (5.1%)
Metabolism and nutrition disorders
Hyperglycaemia	63/229 (27.5%)		20/224 (8.9%)		11/223 (4.9%)		28/223 (12.6%)		49/165 (29.7%)		27/165 (16.4%)		23/168 (13.7%)		56/206 (27.2%)		25/217 (11.5%)		14/214 (6.5%)		59/225 (26.2%)		24/224 (10.7%)		26/217 (12%)
Hypoglycaemia	3/229 (1.3%)		4/224 (1.8%)		2/223 (0.9%)		2/223 (0.9%)		8/165 (4.8%)		4/165 (2.4%)		7/168 (4.2%)		8/206 (3.9%)		15/217 (6.9%)		10/214 (4.7%)		40/225 (17.8%)		53/224 (23.7%)		46/217 (21.2%)
Dyslipidaemia	15/229 (6.6%)		16/224 (7.1%)		14/223 (6.3%)		14/223 (6.3%)		26/165 (15.8%)		23/165 (13.9%)		21/168 (12.5%)		7/206 (3.4%)		16/217 (7.4%)		8/214 (3.7%)		5/225 (2.2%)		5/224 (2.2%)		5/217 (2.3%)
Hypercholesterolaemia	0/229 (0%)		0/224 (0%)		0/223 (0%)		6/223 (2.7%)		3/165 (1.8%)		9/165 (5.5%)		7/168 (4.2%)		1/206 (0.5%)		2/217 (0.9%)		2/214 (0.9%)		1/225 (0.4%)		0/224 (0%)		2/217 (0.9%)
Musculoskeletal and connective tissue disorders
Back pain	11/229 (4.8%)		7/224 (3.1%)		7/223 (3.1%)		18/223 (8.1%)		9/165 (5.5%)		9/165 (5.5%)		7/168 (4.2%)		10/206 (4.9%)		9/217 (4.1%)		11/214 (5.1%)		11/225 (4.9%)		15/224 (6.7%)		12/217 (5.5%)
Arthralgia	11/229 (4.8%)		9/224 (4%)		10/223 (4.5%)		7/223 (3.1%)		9/165 (5.5%)		10/165 (6.1%)		10/168 (6%)		5/206 (2.4%)		7/217 (3.2%)		7/214 (3.3%)		4/225 (1.8%)		11/224 (4.9%)		8/217 (3.7%)
Nervous system disorders
Dizziness	6/229 (2.6%)		6/224 (2.7%)		6/223 (2.7%)		7/223 (3.1%)		6/165 (3.6%)		6/165 (3.6%)		14/168 (8.3%)		6/206 (2.9%)		5/217 (2.3%)		4/214 (1.9%)		16/225 (7.1%)		13/224 (5.8%)		17/217 (7.8%)
Headache	9/229 (3.9%)		10/224 (4.5%)		6/223 (2.7%)		5/223 (2.2%)		8/165 (4.8%)		10/165 (6.1%)		13/168 (7.7%)		7/206 (3.4%)		6/217 (2.8%)		7/214 (3.3%)		13/225 (5.8%)		17/224 (7.6%)		10/217 (4.6%)
Respiratory, thoracic and mediastinal disorders
Cough	6/229 (2.6%)		9/224 (4%)		3/223 (1.3%)		6/223 (2.7%)		6/165 (3.6%)		4/165 (2.4%)		3/168 (1.8%)		7/206 (3.4%)		5/217 (2.3%)		7/214 (3.3%)		3/225 (1.3%)		13/224 (5.8%)		6/217 (2.8%)
Vascular disorders
Hypertension	12/229 (5.2%)		11/224 (4.9%)		5/223 (2.2%)		14/223 (6.3%)		16/165 (9.7%)		6/165 (3.6%)		3/168 (1.8%)		6/206 (2.9%)		7/217 (3.2%)		11/214 (5.1%)		2/225 (0.9%)		6/224 (2.7%)		3/217 (1.4%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.