Empagliflozin (BI 10773) in Type Two Diabetes (T2D) Patients, Open Label Extension

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00881530
• Collaborator: (none)
• Enrollment: 660
• Locations: 137
• Arms: 4
• Patients Per Site: 4.8

Study Details

Study Description

Brief Summary

The objective of the current study is to investigate the safety and efficacy of BI 10773 in 2 different doses compared to Metformin or to Sitagliptin given for 78 weeks in different modalities of treatment in patients with type 2 diabetes mellitus.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: BI 10773; Drug: Metformin; Drug: BI 10773; Drug: Sitagliptin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 660 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 78 Week Open Label Extension to Trials Assessing the Safety and Efficacy of BI 10773 as Monotherapy or in Combination With Metformin in Type 2 Diabetic Patients
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sitagliptin 100 mg	Drug: Sitagliptin; open label comparator
Active Comparator: Metformin 2000 mg	Drug: Metformin; open label comparator
Experimental: BI 10773 X mg lower dose	Drug: BI 10773; BI 10773 low dose once daily
Experimental: BI 10773 Y mg higher dose	Drug: BI 10773; BI 10773 high dose once daily

Outcome Measures

Primary Outcome Measures

1. Hypoglycaemic Events [78 weeks plus 1 week of follow-up]

   Investigator defined Hypoglycaemic events. For documentation of hypoglycemic events, the following criteria were taken into consideration: Asymptomatic hypoglycemia: the event was not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of ≤70 mg/dL (≤3.9 mmol/L) Documented symptomatic hypoglycemia with glucose of ≥54 mg/dL and ≤70 mg/dL (≥3.0 mmol/L and ≤3.9 mmol/L) Documented symptomatic hypoglycemia with glucose of <54 mg/dL (<3.0 mmol/L): the event was accompanied by typical symptoms of hypoglycemia but in no need for external assistance Severe hypoglycemic episode: the event required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions

2. Change From Baseline to Week 78 in Lipid Parameters [Weeks 1 and 78]

   Change from baseline to week 78 in lipid parameters (Total cholesterol, High-density lipoprotein (HDL), Low-density lipoprotein (LDL) and Triglyceride)

3. Clinical Relevant Abnormalities for Physical Examination, Vital Signs, ECG and Laboratory Measurements [78 weeks plus 1 week of follow-up]

   Clinical Relevant Abnormalities for Physical Examination, Vital Signs, ECG and Laboratory Measurements. New abnormal findings or worsening of baseline conditions were reported as treatment related Adverse Events.

Secondary Outcome Measures

1. Change From Baseline in HbA1c Over Time [Weeks 1, 6, 18, 30, 42, 54, 66 and 78]

   Baseline source: before first intake of active treatment (preceding trial or Open label extension)

2. Occurence of a Treat-to-target Response (HbA1c < 7.0%) [Weeks 1, 6, 18, 30, 42, 54, 66 and 78]

   Occurence of a treat-to-target response, defined as HbA1c < 7.0% over time

3. Occurrence of a Treat-to-target Response (HbA1c < 6.5%) [Weeks 1, 6, 18, 30, 42, 54, 66 and 78]

   Occurrence of a Treat-to-target Response, defined as HbA1c < 6.5% over time

4. Occurrence of a Relative Efficacy Response [Weeks 1, 6, 18, 30, 42, 54, 66 and 78]

   Occurrence of a Relative Efficacy Response (HbA1c Lowered by at least >=0.5% over time)

5. Change From Baseline in Fasting Plasma Glucose (FPG) Over Time [Weeks 1, 6, 18, 30, 42, 54, 66 and 78]

   Baseline source: before first intake of active treatment (preceding trial or Open label extension)

Eligibility Criteria

Criteria

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

Inclusion criteria:

• patients completing one of double blind phase II trials 1245.9 or 1245.10

• informed consent

Exclusion criteria:

• patients meeting withdrawal criteria of preceding trial

• significant hepatic impairment

• significant renal impairment with creatinine clearance < 50 ml/min

• contraindication to Metformin for all patients treated with Metformin

• premenopausal women that are nursing or pregnant or not practicing acceptable methods of birth control

• drug or alcohol abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1245.24.101001 Boehringer Ingelheim Investigational Site	Mission Viejo	California	United States
2	1245.24.101028 Boehringer Ingelheim Investigational Site	Spring Valley	California	United States
3	1245.24.101027 Boehringer Ingelheim Investigational Site	Walnut Creek	California	United States
4	1245.24.101004 Boehringer Ingelheim Investigational Site	Clearwarter	Florida	United States
5	1245.24.101005 Boehringer Ingelheim Investigational Site	Miami	Florida	United States
6	1245.24.101024 Boehringer Ingelheim Investigational Site	St. Cloud	Florida	United States
7	1245.24.101014 Boehringer Ingelheim Investigational Site	Roswell	Georgia	United States
8	1245.24.101016 Boehringer Ingelheim Investigational Site	Staten Island	New York	United States
9	1245.24.101006 Boehringer Ingelheim Investigational Site	Wadsworth	Ohio	United States
10	1245.24.101023 Boehringer Ingelheim Investigational Site	Norristown	Pennsylvania	United States
11	1245.24.101015 Boehringer Ingelheim Investigational Site	Dallas	Texas	United States
12	1245.24.101025 Boehringer Ingelheim Investigational Site	Federal Way	Washington	United States
13	1245.24.431002 Boehringer Ingelheim Investigational Site	Graz		Austria
14	1245.24.431001 Boehringer Ingelheim Investigational Site	Wien		Austria
15	1245.24.431003 Boehringer Ingelheim Investigational Site	Wien		Austria
16	1245.24.385104 Boehringer Ingelheim Investigational Site	Karlovac		Croatia
17	1245.24.385103 Boehringer Ingelheim Investigational Site	Krapinske Toplice		Croatia
18	1245.24.385106 Boehringer Ingelheim Investigational Site	Osijek		Croatia
19	1245.24.385101 Boehringer Ingelheim Investigational Site	Zagreb		Croatia
20	1245.24.420101 Boehringer Ingelheim Investigational Site	Breclav		Czech Republic
21	1245.24.420103 Boehringer Ingelheim Investigational Site	Brno		Czech Republic
22	1245.24.420105 Boehringer Ingelheim Investigational Site	Brno		Czech Republic
23	1245.24.420102 Boehringer Ingelheim Investigational Site	Hodonin		Czech Republic
24	1245.24.372101 Boehringer Ingelheim Investigational Site	Tallinn		Estonia
25	1245.24.372102 Boehringer Ingelheim Investigational Site	Tallinn		Estonia
26	1245.24.372103 Boehringer Ingelheim Investigational Site	Tallinn		Estonia
27	1245.24.372104 Boehringer Ingelheim Investigational Site	Tallinn		Estonia
28	1245.24.372105 Boehringer Ingelheim Investigational Site	Tartu		Estonia
29	1245.24.581006 Boehringer Ingelheim Investigational Site	Kerava		Finland
30	1245.24.581003 Boehringer Ingelheim Investigational Site	Oulu		Finland
31	1245.24.581004 Boehringer Ingelheim Investigational Site	Tampere		Finland
32	1245.24.581001 Boehringer Ingelheim Investigational Site	Turku		Finland
33	1245.24.3302A Boehringer Ingelheim Investigational Site	Bondy Cedex		France
34	1245.24.3302B Boehringer Ingelheim Investigational Site	Bondy Cedex		France
35	1245.24.3310A Boehringer Ingelheim Investigational Site	Caen Cedex 5		France
36	1245.24.3310C Boehringer Ingelheim Investigational Site	Caen Cedex 5		France
37	1245.24.3301A Boehringer Ingelheim Investigational Site	Corbeil Essonnes		France
38	1245.24.3303A Boehringer Ingelheim Investigational Site	La Rochelle Cedex 1		France
39	1245.24.3303B Boehringer Ingelheim Investigational Site	La Rochelle Cedex 1		France
40	1245.24.3309A Boehringer Ingelheim Investigational Site	Nanterre Cedex		France
41	1245.24.3306A Boehringer Ingelheim Investigational Site	Narbonne Cedex		France
42	1245.24.3304A Boehringer Ingelheim Investigational Site	Reims Cedex		France
43	1245.24.3311B Boehringer Ingelheim Investigational Site	Saint Mandé		France
44	1245.24.3305A Boehringer Ingelheim Investigational Site	Valenciennes		France
45	1245.24.3305B Boehringer Ingelheim Investigational Site	Valenciennes		France
46	1245.24.491011 Boehringer Ingelheim Investigational Site	Aschaffenburg		Germany
47	1245.24.491007 Boehringer Ingelheim Investigational Site	Frankfurt am Main		Germany
48	1245.24.491004 Boehringer Ingelheim Investigational Site	Hamburg		Germany
49	1245.24.491005 Boehringer Ingelheim Investigational Site	Hamburg		Germany
50	1245.24.491002 Boehringer Ingelheim Investigational Site	Melsungen		Germany
51	1245.24.491012 Boehringer Ingelheim Investigational Site	Nürnberg		Germany
52	1245.24.491008 Boehringer Ingelheim Investigational Site	Rehlingen-Siersburg		Germany
53	1245.24.491003 Boehringer Ingelheim Investigational Site	St. Ingbert/Oberwürzbach		Germany
54	1245.24.491010 Boehringer Ingelheim Investigational Site	Sulzbach-Rosenberg		Germany
55	1245.24.361001 Boehringer Ingelheim Investigational Site	Budapest		Hungary
56	1245.24.361003 Boehringer Ingelheim Investigational Site	Budapest		Hungary
57	1245.24.361004 Boehringer Ingelheim Investigational Site	Budapest		Hungary
58	1245.24.361005 Boehringer Ingelheim Investigational Site	Gyor		Hungary
59	1245.24.361002 Boehringer Ingelheim Investigational Site	Szombathely		Hungary
60	1245.24.391006 Boehringer Ingelheim Investigational Site	Genova		Italy
61	1245.24.391003 Boehringer Ingelheim Investigational Site	Pisa		Italy
62	1245.24.391005 Boehringer Ingelheim Investigational Site	Treviso		Italy
63	1245.24.821006 Boehringer Ingelheim Investigational Site	Goyang		Korea, Republic of
64	1245.24.821008 Boehringer Ingelheim Investigational Site	Goyang		Korea, Republic of
65	1245.24.821007 Boehringer Ingelheim Investigational Site	Incheon		Korea, Republic of
66	1245.24.821002 Boehringer Ingelheim Investigational Site	Pucheon		Korea, Republic of
67	1245.24.821001 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
68	1245.24.821004 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
69	1245.24.821009 Boehringer Ingelheim Investigational Site	Suwon		Korea, Republic of
70	1245.24.821003 Boehringer Ingelheim Investigational Site	Uijeongbu		Korea, Republic of
71	1245.24.371101 Boehringer Ingelheim Investigational Site	Daugavpils		Latvia
72	1245.24.371105 Boehringer Ingelheim Investigational Site	Kuldiga		Latvia
73	1245.24.371106 Boehringer Ingelheim Investigational Site	Ogre		Latvia
74	1245.24.371103 Boehringer Ingelheim Investigational Site	Riga		Latvia
75	1245.24.371107 Boehringer Ingelheim Investigational Site	Riga		Latvia
76	1245.24.371102 Boehringer Ingelheim Investigational Site	Talsi		Latvia
77	1245.24.371104 Boehringer Ingelheim Investigational Site	Valmiera		Latvia
78	1245.24.370102 Boehringer Ingelheim Investigational Site	Klaipeda		Lithuania
79	1245.24.370101 Boehringer Ingelheim Investigational Site	Vilnius		Lithuania
80	1245.24.471003 Boehringer Ingelheim Investigational Site	Hamar		Norway
81	1245.24.471005 Boehringer Ingelheim Investigational Site	Oslo		Norway
82	1245.24.471001 Boehringer Ingelheim Investigational Site	Stavanger		Norway
83	1245.24.471004 Boehringer Ingelheim Investigational Site	Ålesund		Norway
84	1245.24.401005 Boehringer Ingelheim Investigational Site	Alba Iulia		Romania
85	1245.24.401006 Boehringer Ingelheim Investigational Site	Baia Mare Maramures		Romania
86	1245.24.401002 Boehringer Ingelheim Investigational Site	Brasov		Romania
87	1245.24.401001 Boehringer Ingelheim Investigational Site	Bucharest		Romania
88	1245.24.401008 Boehringer Ingelheim Investigational Site	Bucharest		Romania
89	1245.24.401003 Boehringer Ingelheim Investigational Site	Galati		Romania
90	1245.24.401007 Boehringer Ingelheim Investigational Site	Satu Mare		Romania
91	1245.24.401004 Boehringer Ingelheim Investigational Site	Targu-Mures		Romania
92	1245.24.701001 Boehringer Ingelheim Investigational Site	Ekaterinburg		Russian Federation
93	1245.24.701002 Boehringer Ingelheim Investigational Site	Kazan		Russian Federation
94	1245.24.701008 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
95	1245.24.701009 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
96	1245.24.701010 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
97	1245.24.701004 Boehringer Ingelheim Investigational Site	Petrozavodsk		Russian Federation
98	1245.24.701014 Boehringer Ingelheim Investigational Site	Saratov		Russian Federation
99	1245.24.701005 Boehringer Ingelheim Investigational Site	Smolensk		Russian Federation
100	1245.24.701012 Boehringer Ingelheim Investigational Site	St. Petersburg		Russian Federation
101	1245.24.701013 Boehringer Ingelheim Investigational Site	St. Petersburg		Russian Federation
102	1245.24.701006 Boehringer Ingelheim Investigational Site	Yaroslavl		Russian Federation
103	1245.24.701007 Boehringer Ingelheim Investigational Site	Yaroslavl		Russian Federation
104	1245.24.421102 Boehringer Ingelheim Investigational Site	Bratislava		Slovakia
105	1245.24.421107 Boehringer Ingelheim Investigational Site	Bratislava		Slovakia
106	1245.24.421103 Boehringer Ingelheim Investigational Site	Lucenec		Slovakia
107	1245.24.421105 Boehringer Ingelheim Investigational Site	Nitra		Slovakia
108	1245.24.421106 Boehringer Ingelheim Investigational Site	Nitra		Slovakia
109	1245.24.421104 Boehringer Ingelheim Investigational Site	Nove Mesto Nad Vahom		Slovakia
110	1245.24.421108 Boehringer Ingelheim Investigational Site	Presov		Slovakia
111	1245.24.421101 Boehringer Ingelheim Investigational Site	Prievidza		Slovakia
112	1245.24.341002 Boehringer Ingelheim Investigational Site	Barcelona		Spain
113	1245.24.341001 Boehringer Ingelheim Investigational Site	Girona		Spain
114	1245.24.341010 Boehringer Ingelheim Investigational Site	L'Hospitalet de Llobregat (Barcelona)		Spain
115	1245.24.341004 Boehringer Ingelheim Investigational Site	Málaga		Spain
116	1245.24.341005 Boehringer Ingelheim Investigational Site	Palma Mallorca		Spain
117	1245.24.341006 Boehringer Ingelheim Investigational Site	Palma Mallorca		Spain
118	1245.24.341008 Boehringer Ingelheim Investigational Site	Santander		Spain
119	1245.24.461004 Boehringer Ingelheim Investigational Site	Härnösand		Sweden
120	1245.24.461005 Boehringer Ingelheim Investigational Site	Lund		Sweden
121	1245.24.461001 Boehringer Ingelheim Investigational Site	Stockholm		Sweden
122	1245.24.886105 Boehringer Ingelheim Investigational Site	Changhua		Taiwan
123	1245.24.886107 Boehringer Ingelheim Investigational Site	Kaohsiung		Taiwan
124	1245.24.886104 Boehringer Ingelheim Investigational Site	Taichun		Taiwan
125	1245.24.886106 Boehringer Ingelheim Investigational Site	Tainan		Taiwan
126	1245.24.886101 Boehringer Ingelheim Investigational Site	Taipei		Taiwan
127	1245.24.886103 Boehringer Ingelheim Investigational Site	Taipei		Taiwan
128	1245.24.886102 Boehringer Ingelheim Investigational Site	Taoyuan		Taiwan
129	1245.24.381007 Boehringer Ingelheim Investigational Site	Dnepropetrovsk		Ukraine
130	1245.24.381010 Boehringer Ingelheim Investigational Site	Kharkiv		Ukraine
131	1245.24.381003 Boehringer Ingelheim Investigational Site	Kharkov		Ukraine
132	1245.24.381009 Boehringer Ingelheim Investigational Site	Kharkov		Ukraine
133	1245.24.381008 Boehringer Ingelheim Investigational Site	Kiev		Ukraine
134	1245.24.381002 Boehringer Ingelheim Investigational Site	Odessa		Ukraine
135	1245.24.381006 Boehringer Ingelheim Investigational Site	Vinnitsa		Ukraine
136	1245.24.381001 Boehringer Ingelheim Investigational Site	Vinnytsya		Ukraine
137	1245.24.381005 Boehringer Ingelheim Investigational Site	Vinnytsya		Ukraine

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT00881530
• Other Study ID Numbers: 1245.24; 2008-007938-21
• First Posted: Apr 15, 2009
• Last Update Posted: Jun 16, 2014
• Last Verified: May 1, 2014

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

Study Results

Participant Flow

Recruitment Details	This was an open label extension trial of the blinded 12-week dose-finding studies NCT00789035 and NCT00749190.
Pre-assignment Detail	Patients from the preceding empagliflozin 10 and 25 mg groups continued to take the same doses. Patients on placebo and other empagliflozin doses were re-randomised to one of the empagliflozin treatments. Patients on metformin monotherapy or sitagliptin added-on to metformin in the preceding trials continued their open label treatments.

Arm/Group Title	Empagliflozin 10 mg	Empagliflozin 25 mg	Metformin	Empagliflozin 10 mg + Metformin	Empagliflozin 25 mg + Metformin	Sitaglipin + Metformin
Arm/Group Description	Patients receive 10 mg Empagliflozin in tablets once daily.	Patients receive 25 mg Empagliflozin in tablets once daily.	Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.	Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Period Title: Overall Study
STARTED	106	109	56	166	166	56
COMPLETED	92	104	51	157	152	51
NOT COMPLETED	14	5	5	9	14	5

Baseline Characteristics

Arm/Group Title	Empagliflozin 10 mg	Empagliflozin 25 mg	Metformin	Empagliflozin 10 mg + Metformin	Empagliflozin 25 mg + Metformin	Sitaglipin + Metformin	Total
Arm/Group Description	Patients receive 10 mg Empagliflozin in tablets once daily.	Patients receive 25 mg Empagliflozin in tablets once daily.	Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.	Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Total of all reporting groups
Overall Participants	106	109	56	166	166	56	659
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.3 (8.5)	58.5 (10.0)	56.8 (8.9)	58.4 (8.3)	59.9 (7.8)	58.3 (10.5)	58.6 (8.8)
Sex: Female, Male (Count of Participants)
Female	57 53.8%	52 47.7%	28 50%	83 50%	78 47%	27 48.2%	325 49.3%
Male	49 46.2%	57 52.3%	28 50%	83 50%	88 53%	29 51.8%	334 50.7%

Outcome Measures

1. Primary Outcome

Title	Hypoglycaemic Events
Description	Investigator defined Hypoglycaemic events. For documentation of hypoglycemic events, the following criteria were taken into consideration: Asymptomatic hypoglycemia: the event was not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of ≤70 mg/dL (≤3.9 mmol/L) Documented symptomatic hypoglycemia with glucose of ≥54 mg/dL and ≤70 mg/dL (≥3.0 mmol/L and ≤3.9 mmol/L) Documented symptomatic hypoglycemia with glucose of <54 mg/dL (<3.0 mmol/L): the event was accompanied by typical symptoms of hypoglycemia but in no need for external assistance Severe hypoglycemic episode: the event required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions
Time Frame	78 weeks plus 1 week of follow-up

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Empagliflozin 10 mg	Empagliflozin 25 mg	Metformin	Empagliflozin 10 mg + Metformin	Empagliflozin 25 mg + Metformin	Sitaglipin + Metformin
Arm/Group Description	Patients receive 10 mg Empagliflozin in tablets once daily.	Patients receive 25 mg Empagliflozin in tablets once daily.	Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.	Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Measure Participants	106	109	56	166	166	56
Number [percentage of participants]	0.9 0.8%	1.8 1.7%	7.1 12.7%	2.4 1.4%	3.6 2.2%	5.4 9.6%

2. Primary Outcome

Title	Change From Baseline to Week 78 in Lipid Parameters
Description	Change from baseline to week 78 in lipid parameters (Total cholesterol, High-density lipoprotein (HDL), Low-density lipoprotein (LDL) and Triglyceride)
Time Frame	Weeks 1 and 78

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Empagliflozin 10 mg	Empagliflozin 25 mg	Metformin	Empagliflozin 10 mg + Metformin	Empagliflozin 25 mg + Metformin	Sitaglipin + Metformin
Arm/Group Description	Patients receive 10 mg Empagliflozin in tablets once daily.	Patients receive 25 mg Empagliflozin in tablets once daily.	Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.	Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Measure Participants	105	109	56	164	162	56
Total Cholesterol	-0.13 (1.17)	0.09 (0.88)	-0.24 (0.77)	0.19 (0.81)	0.13 (0.75)	-0.05 (0.91)
HDL	0.08 (0.11)	0.07 (0.10)	0.06 (0.10)	0.06 (0.09)	0.07 (0.10)	0.03 (0.08)
LDL (N=102, 108, 52, 161, 159, 55)	-0.02 (0.83)	0.05 (0.83)	-0.13 (0.74)	0.13 (0.71)	0.07 (0.69)	0.00 (0.79)
Triglyceride	-0.5 (2.3)	-0.0 (0.6)	-0.5 (1.2)	0.1 (0.9)	-0.1 (0.8)	-0.2 (0.9)

3. Secondary Outcome

Title	Change From Baseline in HbA1c Over Time
Description	Baseline source: before first intake of active treatment (preceding trial or Open label extension)
Time Frame	Weeks 1, 6, 18, 30, 42, 54, 66 and 78

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Empagliflozin 10 mg	Empagliflozin 25 mg	Metformin	Empagliflozin 10 mg + Metformin	Empagliflozin 25 mg + Metformin	Sitaglipin + Metformin
Arm/Group Description	Patients receive 10 mg Empagliflozin in tablets once daily.	Patients receive 25 mg Empagliflozin in tablets once daily.	Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.	Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Measure Participants	106	109	56	166	166	56
Week 6 (N=104, 108, 55, 162, 163, 54)	-0.40 (0.77)	-0.57 (0.81)	-1.03 (0.76)	-0.36 (0.67)	-0.55 (0.60)	-0.75 (0.80)
Week 18 (N=93, 105, 53, 149, 157, 48)	-0.58 (0.75)	-0.72 (0.88)	-0.92 (0.91)	-0.51 (0.68)	-0.70 (0.68)	-0.79 (0.84)
Week 30 (N=93, 99, 50, 140, 151, 45)	-0.47 (0.85)	-0.61 (0.90)	-0.95 (0.82)	-0.58 (0.69)	-0.76 (0.70)	-0.68 (0.82)
Week 42 (N=85, 93, 46, 132, 140, 44)	-0.59 (0.87)	-0.74 (0.98)	-1.10 (0.80)	-0.65 (0.72)	-0.79 (0.76)	-0.51 (1.03)
Week 54 (N=78, 85, 44, 128, 136, 41)	-0.66 (0.83)	-0.71 (0.87)	-1.13 (0.89)	-0.62 (0.76)	-0.75 (0.73)	-0.79 (0.79)
Week 66 (N=80, 87, 43, 120, 127, 39)	-0.55 (0.80)	-0.71 (1.01)	-1.04 (0.79)	-0.59 (0.79)	-0.73 (0.77)	-0.78 (0.90)
Week 78 (N=72, 84, 42, 115, 121, 38)	-0.50 (0.77)	-0.55 (0.90)	-0.80 (0.88)	-0.56 (0.80)	-0.71 (0.81)	-0.66 (0.99)

4. Secondary Outcome

Title	Occurence of a Treat-to-target Response (HbA1c < 7.0%)
Description	Occurence of a treat-to-target response, defined as HbA1c < 7.0% over time
Time Frame	Weeks 1, 6, 18, 30, 42, 54, 66 and 78

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Empagliflozin 10 mg	Empagliflozin 25 mg	Metformin	Empagliflozin 10 mg + Metformin	Empagliflozin 25 mg + Metformin	Sitaglipin + Metformin
Arm/Group Description	Patients receive 10 mg Empagliflozin in tablets once daily.	Patients receive 25 mg Empagliflozin in tablets once daily.	Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.	Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Measure Participants	106	109	56	166	166	56
Week 6 (N=104, 108, 55, 162, 163, 54)	26.9 25.4%	25.0 22.9%	45.5 81.3%	24.1 14.5%	25.2 15.2%	35.2 62.9%
Week 18 (N=93, 105, 53, 149, 157, 48)	33.3 31.4%	33.3 30.6%	45.3 80.9%	31.5 19%	37.6 22.7%	35.4 63.2%
Week 30 (N=93, 99, 50, 140, 151, 45)	34.4 32.5%	29.3 26.9%	42.0 75%	28.6 17.2%	45.7 27.5%	28.9 51.6%
Week 42 (N=85, 93, 46, 132, 140, 44)	41.2 38.9%	40.9 37.5%	52.2 93.2%	39.4 23.7%	47.1 28.4%	25.0 44.6%
Week 54 (N=78, 85, 44, 128, 136, 41)	43.6 41.1%	32.9 30.2%	56.8 101.4%	35.9 21.6%	47.8 28.8%	29.3 52.3%
Week 66 (N=80, 87, 43, 120, 127, 39)	31.3 29.5%	39.1 35.9%	44.2 78.9%	35.8 21.6%	48.0 28.9%	38.5 68.8%
Week 78 (N=72, 84, 42, 115, 121, 38)	31.9 30.1%	32.1 29.4%	31.0 55.4%	27.0 16.3%	44.6 26.9%	36.8 65.7%

5. Secondary Outcome

Title	Occurrence of a Treat-to-target Response (HbA1c < 6.5%)
Description	Occurrence of a Treat-to-target Response, defined as HbA1c < 6.5% over time
Time Frame	Weeks 1, 6, 18, 30, 42, 54, 66 and 78

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Empagliflozin 10 mg	Empagliflozin 25 mg	Metformin	Empagliflozin 10 mg + Metformin	Empagliflozin 25 mg + Metformin	Sitaglipin + Metformin
Arm/Group Description	Patients receive 10 mg Empagliflozin in tablets once daily.	Patients receive 25 mg Empagliflozin in tablets once daily.	Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.	Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Measure Participants	106	109	56	166	166	56
Week 6 (N=104, 108, 55, 162, 163, 54)	3.8 3.6%	11.1 10.2%	16.4 29.3%	6.2 3.7%	6.7 4%	11.1 19.8%
Week 18 (N=93, 105, 53, 149, 157, 48)	11.8 11.1%	12.4 11.4%	13.2 23.6%	4.7 2.8%	5.1 3.1%	12.5 22.3%
Week 30 (N=93, 99, 50, 140, 151, 45)	8.6 8.1%	10.1 9.3%	14.0 25%	8.6 5.2%	10.6 6.4%	4.4 7.9%
Week 42 (N=85, 93, 46, 132, 140, 44)	11.8 11.1%	10.8 9.9%	21.7 38.8%	10.6 6.4%	21.4 12.9%	9.1 16.3%
Week 54 (N=78, 85, 44, 128, 136, 41)	11.5 10.8%	5.9 5.4%	18.2 32.5%	10.9 6.6%	15.4 9.3%	9.8 17.5%
Week 66 (N=80, 87, 43, 120, 127, 39)	10.0 9.4%	11.5 10.6%	14.0 25%	8.3 5%	12.6 7.6%	15.4 27.5%
Week 78 (N=72, 84, 42, 115, 121, 38)	6.9 6.5%	8.3 7.6%	9.5 17%	10.4 6.3%	13.2 8%	18.4 32.9%

6. Secondary Outcome

Title	Occurrence of a Relative Efficacy Response
Description	Occurrence of a Relative Efficacy Response (HbA1c Lowered by at least >=0.5% over time)
Time Frame	Weeks 1, 6, 18, 30, 42, 54, 66 and 78

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Empagliflozin 10 mg	Empagliflozin 25 mg	Metformin	Empagliflozin 10 mg + Metformin	Empagliflozin 25 mg + Metformin	Sitaglipin + Metformin
Arm/Group Description	Patients receive 10 mg Empagliflozin in tablets once daily.	Patients receive 25 mg Empagliflozin in tablets once daily.	Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.	Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Measure Participants	106	109	56	166	166	56
Week 6 (N=104, 108, 55, 162, 163, 54)	42.3 39.9%	50.9 46.7%	80.0 142.9%	41.4 24.9%	56.4 34%	63.0 112.5%
Week 18 (N=93, 105, 53, 149, 157, 48)	51.6 48.7%	61.9 56.8%	77.4 138.2%	53.7 32.3%	61.8 37.2%	66.7 119.1%
Week 30 (N=93, 99, 50, 140, 151, 45)	50.5 47.6%	55.6 51%	78.0 139.3%	55.0 33.1%	63.6 38.3%	68.9 123%
Week 42 (N=85, 93, 46, 132, 140, 44)	58.8 55.5%	60.2 55.2%	82.6 147.5%	62.1 37.4%	66.4 40%	54.5 97.3%
Week 54 (N=78, 85, 44, 128, 136, 41)	62.8 59.2%	58.8 53.9%	81.8 146.1%	59.4 35.8%	65.4 39.4%	58.5 104.5%
Week 66 (N=80, 87, 43, 120, 127, 39)	53.8 50.8%	56.3 51.7%	76.7 137%	55.0 33.1%	64.6 38.9%	66.7 119.1%
Week 78 (N=72, 84, 42, 115, 121, 38)	50.0 47.2%	50.0 45.9%	66.7 119.1%	56.5 34%	64.5 38.9%	60.5 108%

7. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) Over Time
Description	Baseline source: before first intake of active treatment (preceding trial or Open label extension)
Time Frame	Weeks 1, 6, 18, 30, 42, 54, 66 and 78

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Empagliflozin 10 mg	Empagliflozin 25 mg	Metformin	Empagliflozin 10 mg + Metformin	Empagliflozin 25 mg + Metformin	Sitaglipin + Metformin
Arm/Group Description	Patients receive 10 mg Empagliflozin in tablets once daily.	Patients receive 25 mg Empagliflozin in tablets once daily.	Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.	Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Measure Participants	106	109	56	166	166	56
Week 6 (N=102, 108, 55, 156, 160, 53)	-30.6 (42.5)	-35.8 (39.6)	-29.9 (40.0)	-25.7 (35.2)	-36.7 (36.3)	-32.6 (42.4)
Week 18 (N=94, 103, 51, 144, 153, 45)	-35.5 (37.9)	-33.7 (42.0)	-30.4 (40.3)	-30.6 (31.6)	-37.6 (35.8)	-16.7 (44.0)
Week 30 (N=92, 101, 51, 133, 147, 43)	-32.3 (41.4)	-35.0 (39.6)	-28.5 (28.9)	-29.9 (34.9)	-37.9 (38.6)	-25.6 (38.6)
Week 42 (N=85, 93, 46, 126, 140, 42)	-35.8 (39.1)	-31.3 (41.4)	-31.0 (35.6)	-30.8 (36.4)	-36.8 (34.1)	-18.5 (43.1)
Week 54 (N=80, 88, 44, 124, 134, 39)	-32.1 (37.2)	-31.0 (37.8)	-31.8 (35.9)	-28.2 (33.7)	-36.8 (32.5)	-29.4 (35.4)
Week 66 (N=80, 86, 43, 116, 125, 38)	-28.0 (41.4)	-28.6 (42.6)	-26.4 (35.7)	-21.7 (36.2)	-29.6 (36.4)	-32.5 (46.9)
Week 78 (N=72, 84, 43, 112, 121, 36)	-27.9 (33.1)	-25.4 (40.9)	-22.9 (39.7)	-24.7 (41.5)	-31.9 (36.5)	-25.7 (48.9)

8. Primary Outcome

Title	Clinical Relevant Abnormalities for Physical Examination, Vital Signs, ECG and Laboratory Measurements
Description	Clinical Relevant Abnormalities for Physical Examination, Vital Signs, ECG and Laboratory Measurements. New abnormal findings or worsening of baseline conditions were reported as treatment related Adverse Events.
Time Frame	78 weeks plus 1 week of follow-up

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Empagliflozin 10 mg	Empagliflozin 25 mg	Metformin	Empagliflozin 10 mg + Metformin	Empagliflozin 25 mg + Metformin	Sitaglipin + Metformin
Arm/Group Description	Patients receive 10 mg Empagliflozin in tablets once daily.	Patients receive 25 mg Empagliflozin in tablets once daily.	Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.	Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.	Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
Measure Participants	106	109	56	166	166	56
Alanine aminotransferase increased	0.9 0.8%	0.9 0.8%	3.6 6.4%	0.6 0.4%	0.6 0.4%	1.8 3.2%
Aspartate aminotransferase increased	1.9 1.8%	0.0 0%	1.8 3.2%	0.0 0%	0.6 0.4%	0.0 0%
Gamma-glutamyltransferase increased	0.9 0.8%	0.0 0%	1.8 3.2%	0.0 0%	1.2 0.7%	0.0 0%
Blood alkaline phosphatase increased	0.9 0.8%	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Blood creatine phosphokinase increased	0.9 0.8%	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Granulocyte count decreased	0.9 0.8%	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Hepatic enzyme increased	0.0 0%	0.9 0.8%	0.0 0%	0.6 0.4%	0.0 0%	0.0 0%
Blood creatinine increased	0.9 0.8%	0.9 0.8%	0.0 0%	0.0 0%	0.6 0.4%	0.0 0%
Creatinine renal clearance decreased	0.0 0%	0.0 0%	0.0 0%	0.6 0.4%	0.0 0%	0.0 0%
Weight decreased	0.0 0%	0.9 0.8%	0.0 0%	0.0 0%	0.6 0.4%	0.0 0%
Sick sinus syndrome	0.9 0.8%	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 0%
Tachycardia	0.9 0.8%	1.8 1.7%	0.0 0%	0.6 0.4%	0.6 0.4%	0.0 0%

Adverse Events

Time Frame	From drug administration until 7 days after the last intake of study drug, up to 582 days
Arm/Group Title	Empagliflozin 10 mg		Empagliflozin 25 mg		Metformin		Empagliflozin 10 mg + Metformin		Empagliflozin 25 mg + Metformin		Sitaglipin + Metformin
Arm/Group Description	Patients receive 10 mg Empagliflozin in tablets once daily.		Patients receive 25 mg Empagliflozin in tablets once daily.		Patients receive between 1000 and 2000 mg Metformin daily as monotherapy. Patients on metformin as active comparator (from trial NCT00789035) were to take their medication according to the instruction of their investigator, continuing the maximum tolerated dose determined in the preceding trial.		Patients receive 10 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.		Patients receive 25 mg Empagliflozin in tablets once daily added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.		Patients receive 100 mg Sitagliptin once daily in tablets added to metformin background. Patients on metformin background (from trial NCT00749190) continued with their standard metformin therapy throughout the entire study.
All Cause Mortality
	Empagliflozin 10 mg		Empagliflozin 25 mg		Metformin		Empagliflozin 10 mg + Metformin		Empagliflozin 25 mg + Metformin		Sitaglipin + Metformin
	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)
Serious Adverse Events
	Empagliflozin 10 mg		Empagliflozin 25 mg		Metformin		Empagliflozin 10 mg + Metformin		Empagliflozin 25 mg + Metformin		Sitaglipin + Metformin
	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	10/106 (9.4%)		7/109 (6.4%)		3/56 (5.4%)		10/166 (6%)		13/166 (7.8%)		9/56 (16.1%)
Blood and lymphatic system disorders
Anaemia	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Cardiac disorders
Angina pectoris	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		1/56 (1.8%)
Angina unstable	0/106 (0%)		0/109 (0%)		0/56 (0%)		1/166 (0.6%)		1/166 (0.6%)		1/56 (1.8%)
Atrial fibrillation	0/106 (0%)		1/109 (0.9%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Myocardial infarction	0/106 (0%)		1/109 (0.9%)		0/56 (0%)		1/166 (0.6%)		0/166 (0%)		0/56 (0%)
Palpitations	0/106 (0%)		1/109 (0.9%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Coronary artery disease	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		1/166 (0.6%)		0/56 (0%)
Myocardial ischaemia	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Ear and labyrinth disorders
Vertigo	0/106 (0%)		1/109 (0.9%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Endocrine disorders
Goitre	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		1/166 (0.6%)		0/56 (0%)
Thyroid cyst	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Eye disorders
Visual acuity reduced	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Gastrointestinal disorders
Colonic polyp	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		1/56 (1.8%)
Abdominal hernia	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Anal fistula	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Gingival cyst	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Inguinal hernia	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Lumbar hernia	0/106 (0%)		0/109 (0%)		0/56 (0%)		1/166 (0.6%)		0/166 (0%)		0/56 (0%)
General disorders
Death	0/106 (0%)		0/109 (0%)		1/56 (1.8%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Non-cardiac chest pain	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		1/166 (0.6%)		0/56 (0%)
Pyrexia	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		1/166 (0.6%)		0/56 (0%)
Hepatobiliary disorders
Cholecystitis acute	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		1/166 (0.6%)		2/56 (3.6%)
Cholelithiasis	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		1/166 (0.6%)		0/166 (0%)		1/56 (1.8%)
Bile duct obstruction	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Cholecystitis	0/106 (0%)		0/109 (0%)		0/56 (0%)		1/166 (0.6%)		0/166 (0%)		0/56 (0%)
Infections and infestations
Cellulitis	0/106 (0%)		1/109 (0.9%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Anal abscess	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		1/166 (0.6%)		0/56 (0%)
Gastroenteritis	0/106 (0%)		0/109 (0%)		0/56 (0%)		1/166 (0.6%)		0/166 (0%)		0/56 (0%)
Post procedural infection	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		1/166 (0.6%)		0/56 (0%)
Pneumonia	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Injury, poisoning and procedural complications
Traumatic fracture	0/106 (0%)		0/109 (0%)		1/56 (1.8%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Fall	0/106 (0%)		1/109 (0.9%)		0/56 (0%)		0/166 (0%)		1/166 (0.6%)		0/56 (0%)
Fibula fracture	0/106 (0%)		1/109 (0.9%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Ligament rupture	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Post procedural haematuria	0/106 (0%)		1/109 (0.9%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Vascular graft occlusion	0/106 (0%)		1/109 (0.9%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Wrist fracture	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Concussion	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		1/166 (0.6%)		0/56 (0%)
Burns second degree	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Meniscus lesion	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Post procedural haematoma	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		2/56 (3.6%)
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		1/56 (1.8%)
Osteoarthritis	0/106 (0%)		0/109 (0%)		0/56 (0%)		1/166 (0.6%)		1/166 (0.6%)		0/56 (0%)
Rotator cuff syndrome	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		1/166 (0.6%)		0/56 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/106 (0%)		0/109 (0%)		1/56 (1.8%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Cervix carcinoma recurrent	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		1/56 (1.8%)
Refractory cytopenia with multilineage dysplasia	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		1/56 (1.8%)
Transitional cell carcinoma	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		1/56 (1.8%)
Bile duct cancer	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Prostate cancer	0/106 (0%)		0/109 (0%)		0/56 (0%)		1/166 (0.6%)		0/166 (0%)		0/56 (0%)
Chronic lymphocytic leukaemia	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Nervous system disorders
Cerebral infarction	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		2/56 (3.6%)
Aphasia	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		1/56 (1.8%)
Hemiplegia	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		1/56 (1.8%)
Ischaemic stroke	0/106 (0%)		0/109 (0%)		0/56 (0%)		1/166 (0.6%)		0/166 (0%)		1/56 (1.8%)
Transient ischaemic attack	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		2/166 (1.2%)		0/56 (0%)
Cerebrovascular accident	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Carotid artery stenosis	0/106 (0%)		0/109 (0%)		0/56 (0%)		1/166 (0.6%)		1/166 (0.6%)		0/56 (0%)
Renal and urinary disorders
Urinary retention	0/106 (0%)		1/109 (0.9%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/106 (1.9%)		1/109 (0.9%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		1/56 (1.8%)
Surgical and medical procedures
Hysterectomy	0/106 (0%)		0/109 (0%)		0/56 (0%)		1/166 (0.6%)		0/166 (0%)		0/56 (0%)
Abortion induced	0/106 (0%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Vascular disorders
Hypertension	1/106 (0.9%)		0/109 (0%)		0/56 (0%)		0/166 (0%)		0/166 (0%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	Empagliflozin 10 mg		Empagliflozin 25 mg		Metformin		Empagliflozin 10 mg + Metformin		Empagliflozin 25 mg + Metformin		Sitaglipin + Metformin
	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	34/106 (32.1%)		46/109 (42.2%)		27/56 (48.2%)		74/166 (44.6%)		79/166 (47.6%)		26/56 (46.4%)
Gastrointestinal disorders
Nausea	2/106 (1.9%)		2/109 (1.8%)		3/56 (5.4%)		6/166 (3.6%)		6/166 (3.6%)		4/56 (7.1%)
Diarrhoea	2/106 (1.9%)		3/109 (2.8%)		3/56 (5.4%)		3/166 (1.8%)		4/166 (2.4%)		1/56 (1.8%)
General disorders
Chest pain	2/106 (1.9%)		0/109 (0%)		3/56 (5.4%)		2/166 (1.2%)		0/166 (0%)		1/56 (1.8%)
Fatigue	0/106 (0%)		1/109 (0.9%)		1/56 (1.8%)		1/166 (0.6%)		1/166 (0.6%)		3/56 (5.4%)
Infections and infestations
Nasopharyngitis	10/106 (9.4%)		8/109 (7.3%)		9/56 (16.1%)		12/166 (7.2%)		15/166 (9%)		5/56 (8.9%)
Urinary tract infection	3/106 (2.8%)		4/109 (3.7%)		1/56 (1.8%)		12/166 (7.2%)		18/166 (10.8%)		5/56 (8.9%)
Bronchitis	2/106 (1.9%)		3/109 (2.8%)		2/56 (3.6%)		2/166 (1.2%)		8/166 (4.8%)		6/56 (10.7%)
Upper respiratory tract infection	5/106 (4.7%)		8/109 (7.3%)		1/56 (1.8%)		3/166 (1.8%)		2/166 (1.2%)		1/56 (1.8%)
Viral infection	0/106 (0%)		7/109 (6.4%)		1/56 (1.8%)		1/166 (0.6%)		0/166 (0%)		0/56 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	12/106 (11.3%)		16/109 (14.7%)		8/56 (14.3%)		36/166 (21.7%)		25/166 (15.1%)		9/56 (16.1%)
Hypoglycaemia	1/106 (0.9%)		2/109 (1.8%)		4/56 (7.1%)		4/166 (2.4%)		6/166 (3.6%)		3/56 (5.4%)
Nervous system disorders
Headache	1/106 (0.9%)		7/109 (6.4%)		4/56 (7.1%)		6/166 (3.6%)		7/166 (4.2%)		0/56 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/106 (0.9%)		3/109 (2.8%)		0/56 (0%)		1/166 (0.6%)		0/166 (0%)		3/56 (5.4%)
Vascular disorders
Hypertension	4/106 (3.8%)		3/109 (2.8%)		4/56 (7.1%)		5/166 (3%)		2/166 (1.2%)		4/56 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

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.