30 Week Parallel Group Comparison Study of Linagliptin + Pioglitazone (5+15, 5+30 and 5+45 mg) qd Versus Respective Monotherapies, Followed by a Comparison of 5mg+30mg and 5mg+45mg Versus Respective Monotherapies in Type 2 Diabetes for up to 54 Weeks

Sponsor

Boehringer Ingelheim (Industry)

Overall Status

Completed

CT.gov ID

NCT01183013

Collaborator

Eli Lilly and Company (Industry)

936

Enrollment

132

Locations

Arms

30.1

Duration (Months)

7.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective is to demonstrate superior glycaemic control (HbA1c reduction) after 30 weeks of linagliptin/pioglitazone (5/15, 5/30 and 5/45 mg) versus the respective individual monotherapies of pioglitazone (15 mg, 30 mg, or 45 mg, administered orally once daily), and linagliptin (5 mg, administered orally once daily). In addition, durability of treatment effect and safety under chronic treatment conditions will be investigated.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Pioglitazone 15 mg Drug: Pioglitazone 45 mg Drug: Pioglitazone 30 mg Drug: Linagliptin 5mg / Pioglitazone 45 mg FDC Drug: Linagliptin 5mg / Pioglitazone 30 mg FDC Drug: Linagliptin 5mg Drug: Linagliptin 5mg / Pioglitazone 15 mg FDC	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

936 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

A Randomised, Double-blind Parallel Group Study to Compare the Efficacy and Safety of Initial Combination Therapy With Linagliptin 5 mg + Pioglitazone 15 mg, 30 mg, or 45 mg, vs. Monotherapy With Pioglitazone (15 mg, 30 mg, or 45 mg) or Linagliptin 5 mg Once Daily for 30 Weeks, Followed by a Blinded Trial Period on Linagliptin 5 mg + Pioglitazone 30 or 45 mg Versus Pioglitazone Monotherapy 30 or 45 mg or Linagliptin 5 mg for up to 54 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control on Diet and Exercise

Study Start Date :

Aug 1, 2010

Actual Primary Completion Date :

Feb 1, 2013

Actual Study Completion Date :

Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Pioglitazone 15 mg Pioglitazone Capsules 15 mg once daily	Drug: Pioglitazone 15 mg Pioglitazone Capsules 15 mg once daily for 30 weeks followed by Pioglitazone Capsules 30 mg once daily for up to 54 weeks
Active Comparator: Pioglitazone 30 mg Pioglitazone Capsules 30 mg once daily	Drug: Pioglitazone 30 mg Pioglitazone Capsules 30 mg once daily for up to 84 weeks
Active Comparator: Pioglitazone 45 mg Pioglitazone Capsules 45 mg once daily	Drug: Pioglitazone 45 mg Pioglitazone Capsules 30 mg once daily for 6 weeks followed by Pioglitazone Capsules 45 mg once daily for up to 78 weeks
Active Comparator: Linagliptin 5mg Linagliptin 5mg Tablets once daily	Drug: Linagliptin 5mg Linagliptin 5mg Tablets low dose once daily for 30 weeks followed by Linagliptin 5mg low dose / Pioglitazone 30 mg FDC Tablets once daily for up to 54 weeks
Experimental: Linagliptin 5mg / Pioglitazone 15 mg Linagliptin 5mg / Pioglitazone 15 mg Tablets once daily	Drug: Linagliptin 5mg / Pioglitazone 15 mg FDC Linagliptin 5mg low dose / Pioglitazone 15 mg FDC Tablets once daily for 30 weeks followed by Linagliptin 5mg low dose / Pioglitazone 30 mg FDC Tablets once daily for up to 54 weeks
Experimental: Linagliptin 5mg / Pioglitazone 30 mg Linagliptin 5mg / Pioglitazone 30 mg Tablets once daily	Drug: Linagliptin 5mg / Pioglitazone 30 mg FDC Linagliptin 5mg low dose / Pioglitazone 30 mg FDC Tablets once daily for up to 84 weeks
Experimental: Linagliptin 5mg / Pioglitazone 45 mg Linagliptin 5mg / Pioglitazone 45 mg Tablets once daily	Drug: Linagliptin 5mg / Pioglitazone 45 mg FDC Linagliptin 5mg low dose / Pioglitazone 30 mg Tablets once daily for 6 weeks followed by Linagliptin 5mg low dose / Pioglitazone 45 mg FDC Tablets once daily for up to 78 weeks

Outcome Measures

Primary Outcome Measures

Change From Baseline in HbA1c After 30 Weeks of Treatment. [Baseline and 30 weeks]
HbA1c is measured as a percentage. The change from baseline is the Week 30 HbA1c minus the baseline HbA1c.

Secondary Outcome Measures

Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 7.0% After 30 Weeks of Treatment [Baseline and 30 weeks]
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin.
Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 6.5% After 30 Weeks of Treatment [Baseline and 30 weeks]
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin.
Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 30 Weeks of Treatment) [Baseline and 30 weeks]
Glycosylated hemoglobin is reported as a percentage of the total hemoglobin.
HbA1c Change From Baseline by Visit Over Time [Baseline, week 6, week 12, week 18, week 24, week 30]
HbA1c is measured as a percentage. The change from baseline is the HbA1c over time minus the baseline HbA1c. The model includes fixed effects for treatment, continuous baseline HbA1c, prior andi-diabetic medication, country, visit and treatment. by visit interaction.
Fasting Plasma Glucose (FPG) Change From Baseline After 30 Weeks of Treatment [Baseline and 30 weeks]
The change from baseline is the FPG after 30 weeks minus the baseline FPG.
Fasting Plasma Glucose (FPG) Change From Baseline by Visit Over Time [Baseline, week 6, week 12, week 18, week 24, week 30]
The change from baseline is the FPG over time minus the baseline FPG. Model includes fixed effects for treatment, continuous baseline FPG, continuous baseline HbA1c, prior anti-diabetic medication, country, visit and treatment by visit interaction
Two-hour Postprandial Glucose (2hPPG) Change From Baseline at Week 30 by Meal Tolerance Test (MTT) [Baseline and 30 weeks]
The change from baseline is the 2hPPG after 30 weeks minus the baseline 2hPPG.
Time to First Use of Rescue Therapy [30 weeks]
Proportion of patients at 30 weeks with rescue therapy using Kaplan-Meier analysis.
Incidence of Rescue Therapy During the First 30 Weeks of Treatment [30 weeks]
Rescue therapy was defined to include any new antidiabetic medication taken for hyperglycemia and introduced on or after the start date of study treatment and before the end date of study treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Diagnosis of type 2 diabetes mellitus prior to informed consent
Male and female patients with insufficient glycaemic control (HbA1c >= 7.0 to <= 10.5% at Visit 2) on diet and exercise alone, without oral antidiabetic drug therapy within 10 weeks prior to start of the run-in period (date of Visit 2)
Age >= 18 and <= 80 years at start date of Visit 1 (Screening)
BMI <= 45 kg/m2 (Body Mass Index) at start date of Visit 1 (Screening)
Signed and dated written informed consent by start date of Visit 1 in accordance with GCP and local legislation

Exclusion criteria:

Uncontrolled hyperglycaemia with a confirmed glucose level > 240 mg/dl (> 13.3 mmol/l) after an overnight fast during screening or placebo run-in period (cf. Section 3.3.4.1)
Myocardial infarction within 6 months, stroke or TIA within 3 months prior to informed consent
Clinical evidence of active liver disease (e.g. jaundice) or the ALT level > 2.5 times the upper limit of normal (according to pioglitazone label)
Bariatric surgery, performed within the past 2 years prior to informed consent or planned at the time of informed consent
Gastrointestinal surgeries prior to informed consent that induce chronic malabsorption
Known hypersensitivity or allergy to the investigational products (linagliptin and/or pioglitazone) or their excipients (including matching placebos)
Contraindications to pioglitazone as defined in the local prescribing information (SPC), particularly :

Diagnose of heart failure or history of heart failure
Haemodialysis patients, due to limited experience with pioglitazone

Treatment with gemfibrozil, montelukast, trimethoprim, or rifampicin - according to pioglitazone label and respective restrictions in Section 4.2.2
Treatment with rosiglitazone, pioglitazone, GLP-1 analogues, or insulin within 3 months prior to informed consent
Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent
Alcohol or drug abuse within the 3 months prior to informed consent or history of alcoholism
Current treatment with systemic corticosteroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
Participation in another trial with an investigational drug within 30 days prior to informed consent
Any other clinical condition as judged by the investigator that would not allow the safe completion of the protocol, e.g. inability of patients to comply with study procedures
Pre-menopausal women (last menstruation <= 1 year prior to informed consent) who:

are nursing or pregnant or
are of child-bearing potential (i.e. not permanently sterilised) and are not practicing a highly effective 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.

A highly effective method of birth control is defined - according to the Note for Guidance on non-clinical safety studies for the conduct of human trials for pharmaceuticals (CPMP/ICH/286/95, modification) - as those which result in a low failure rate (i. e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices/systems (IUDs/IUSs), sexual abstinence or vasectomised partner

Symptomatic gallbladder disease in the last six months
Medical history of pancreatitis.
Patients with urinary bladder cancer or a history of urinary bladder cancer or uninvestigated macroscopic haematuria
Any other contraindication or restriction for use of pioglitazone in accordance with the local prescribing information for pioglitazone.

Contacts and Locations

Locations

	Site	City	State	Country
1	1264.3.01026 Boehringer Ingelheim Investigational Site	Birmingham	Alabama	United States
2	1264.3.01021 Boehringer Ingelheim Investigational Site	Montgomery	Alabama	United States
3	1264.3.01020 Boehringer Ingelheim Investigational Site	Muscle Shoals	Alabama	United States
4	1264.3.01062 Boehringer Ingelheim Investigational Site	Chandler	Arizona	United States
5	1264.3.01064 Boehringer Ingelheim Investigational Site	Mesa	Arizona	United States
6	1264.3.01049 Boehringer Ingelheim Investigational Site	Carmichael	California	United States
7	1264.3.01078 Boehringer Ingelheim Investigational Site	Chino	California	United States
8	1264.3.01031 Boehringer Ingelheim Investigational Site	Concord	California	United States
9	1264.3.01037 Boehringer Ingelheim Investigational Site	Lakewood	California	United States
10	1264.3.01065 Boehringer Ingelheim Investigational Site	Los Angeles	California	United States
11	1264.3.01006 Boehringer Ingelheim Investigational Site	Norwalk	California	United States
12	1264.3.01001 Boehringer Ingelheim Investigational Site	Rancho Cucamonga	California	United States
13	1264.3.01059 Boehringer Ingelheim Investigational Site	San Diego	California	United States
14	1264.3.01023 Boehringer Ingelheim Investigational Site	Tarzana	California	United States
15	1264.3.01016 Boehringer Ingelheim Investigational Site	Tustin	California	United States
16	1264.3.01058 Boehringer Ingelheim Investigational Site	Valencia	California	United States
17	1264.3.01083 Boehringer Ingelheim Investigational Site	Westlake Village	California	United States
18	1264.3.01027 Boehringer Ingelheim Investigational Site	Denver	Colorado	United States
19	1264.3.01033 Boehringer Ingelheim Investigational Site	Norwalk	Connecticut	United States
20	1264.3.01035 Boehringer Ingelheim Investigational Site	Boca Raton	Florida	United States
21	1264.3.01015 Boehringer Ingelheim Investigational Site	Clearwater	Florida	United States
22	1264.3.01082 Boehringer Ingelheim Investigational Site	Hialeah	Florida	United States
23	1264.3.01036 Boehringer Ingelheim Investigational Site	Jacksonville	Florida	United States
24	1264.3.01013 Boehringer Ingelheim Investigational Site	Longwood	Florida	United States
25	1264.3.01038 Boehringer Ingelheim Investigational Site	Miami	Florida	United States
26	1264.3.01042 Boehringer Ingelheim Investigational Site	Miami	Florida	United States
27	1264.3.01079 Boehringer Ingelheim Investigational Site	Miami	Florida	United States
28	1264.3.01019 Boehringer Ingelheim Investigational Site	Port Orange	Florida	United States
29	1264.3.01018 Boehringer Ingelheim Investigational Site	St. Cloud	Florida	United States
30	1264.3.01009 Boehringer Ingelheim Investigational Site	Tampa	Florida	United States
31	1264.3.01012 Boehringer Ingelheim Investigational Site	Tampa	Florida	United States
32	1264.3.01008 Boehringer Ingelheim Investigational Site	Atlanta	Georgia	United States
33	1264.3.01055 Boehringer Ingelheim Investigational Site	Atlanta	Georgia	United States
34	1264.3.01061 Boehringer Ingelheim Investigational Site	Atlanta	Georgia	United States
35	1264.3.01074 Boehringer Ingelheim Investigational Site	Blue Ridge	Georgia	United States
36	1264.3.01084 Boehringer Ingelheim Investigational Site	Cartersville	Georgia	United States
37	1264.3.01060 Boehringer Ingelheim Investigational Site	Perry	Georgia	United States
38	1264.3.01050 Boehringer Ingelheim Investigational Site	Savannah	Georgia	United States
39	1264.3.01077 Boehringer Ingelheim Investigational Site	Chicago	Illinois	United States
40	1264.3.01052 Boehringer Ingelheim Investigational Site	Brownsburg	Indiana	United States
41	1264.3.01075 Boehringer Ingelheim Investigational Site	Evansville	Indiana	United States
42	1264.3.01076 Boehringer Ingelheim Investigational Site	Evansville	Indiana	United States
43	1264.3.01073 Boehringer Ingelheim Investigational Site	Franklin	Indiana	United States
44	1264.3.01002 Boehringer Ingelheim Investigational Site	Wichita	Kansas	United States
45	1264.3.01007 Boehringer Ingelheim Investigational Site	Wichita	Kansas	United States
46	1264.3.01010 Boehringer Ingelheim Investigational Site	Lexington	Kentucky	United States
47	1264.3.01028 Boehringer Ingelheim Investigational Site	New Orleans	Louisiana	United States
48	1264.3.01029 Boehringer Ingelheim Investigational Site	Sunset	Louisiana	United States
49	1264.3.01069 Boehringer Ingelheim Investigational Site	Hyattsville	Maryland	United States
50	1264.3.01066 Boehringer Ingelheim Investigational Site	Southfield	Michigan	United States
51	1264.3.01057 Boehringer Ingelheim Investigational Site	Great Falls	Montana	United States
52	1264.3.01045 Boehringer Ingelheim Investigational Site	Burlington	North Carolina	United States
53	1264.3.01044 Boehringer Ingelheim Investigational Site	Charlotte	North Carolina	United States
54	1264.3.01022 Boehringer Ingelheim Investigational Site	Zanesville	Ohio	United States
55	1264.3.01032 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma	United States
56	1264.3.01051 Boehringer Ingelheim Investigational Site	Fleetwood	Pennsylvania	United States
57	1264.3.01025 Boehringer Ingelheim Investigational Site	Pittsburgh	Pennsylvania	United States
58	1264.3.01081 Boehringer Ingelheim Investigational Site	Columbia	South Carolina	United States
59	1264.3.01003 Boehringer Ingelheim Investigational Site	Greer	South Carolina	United States
60	1264.3.01011 Boehringer Ingelheim Investigational Site	Kingsport	Tennessee	United States
61	1264.3.01017 Boehringer Ingelheim Investigational Site	Corpus Christi	Texas	United States
62	1264.3.01067 Boehringer Ingelheim Investigational Site	Dallas	Texas	United States
63	1264.3.01004 Boehringer Ingelheim Investigational Site	Houston	Texas	United States
64	1264.3.01039 Boehringer Ingelheim Investigational Site	Houston	Texas	United States
65	1264.3.01041 Boehringer Ingelheim Investigational Site	Houston	Texas	United States
66	1264.3.01047 Boehringer Ingelheim Investigational Site	Houston	Texas	United States
67	1264.3.01070 Boehringer Ingelheim Investigational Site	Houston	Texas	United States
68	1264.3.01040 Boehringer Ingelheim Investigational Site	Killeen	Texas	United States
69	1264.3.01048 Boehringer Ingelheim Investigational Site	Midland	Texas	United States
70	1264.3.01030 Boehringer Ingelheim Investigational Site	New Braunfels	Texas	United States
71	1264.3.01071 Boehringer Ingelheim Investigational Site	North Richland Hills	Texas	United States
72	1264.3.01085 Boehringer Ingelheim Investigational Site	Plano	Texas	United States
73	1264.3.01046 Boehringer Ingelheim Investigational Site	San Antonio	Texas	United States
74	1264.3.01056 Boehringer Ingelheim Investigational Site	Norfolk	Virginia	United States
75	1264.3.37207 Boehringer Ingelheim Investigational Site	Harju		Estonia
76	1264.3.37209 Boehringer Ingelheim Investigational Site	Pärnu		Estonia
77	1264.3.37201 Boehringer Ingelheim Investigational Site	Tallinn		Estonia
78	1264.3.37202 Boehringer Ingelheim Investigational Site	Tallinn		Estonia
79	1264.3.37208 Boehringer Ingelheim Investigational Site	Tallinn		Estonia
80	1264.3.37203 Boehringer Ingelheim Investigational Site	Tallin		Estonia
81	1264.3.37204 Boehringer Ingelheim Investigational Site	Tallin		Estonia
82	1264.3.37205 Boehringer Ingelheim Investigational Site	Tallin		Estonia
83	1264.3.37206 Boehringer Ingelheim Investigational Site	Tartu		Estonia
84	1264.3.37210 Boehringer Ingelheim Investigational Site	Viljandi County		Estonia
85	1264.3.49001 Boehringer Ingelheim Investigational Site	Bad Lauterberg / Harz		Germany
86	1264.3.49007 Boehringer Ingelheim Investigational Site	Dietzenbach		Germany
87	1264.3.49002 Boehringer Ingelheim Investigational Site	Dortmund		Germany
88	1264.3.49009 Boehringer Ingelheim Investigational Site	Essen		Germany
89	1264.3.49003 Boehringer Ingelheim Investigational Site	Hamburg		Germany
90	1264.3.49012 Boehringer Ingelheim Investigational Site	Ingelheim		Germany
91	1264.3.49008 Boehringer Ingelheim Investigational Site	Leipzig		Germany
92	1264.3.49005 Boehringer Ingelheim Investigational Site	Mainz		Germany
93	1264.3.49010 Boehringer Ingelheim Investigational Site	Offenbach		Germany
94	1264.3.49004 Boehringer Ingelheim Investigational Site	Stuhr		Germany
95	1264.3.37105 Boehringer Ingelheim Investigational Site	Daugavpils		Latvia
96	1264.3.37112 Boehringer Ingelheim Investigational Site	Daugavpils		Latvia
97	1264.3.37113 Boehringer Ingelheim Investigational Site	Daugavpils		Latvia
98	1264.3.37110 Boehringer Ingelheim Investigational Site	Jelgava		Latvia
99	1264.3.37101 Boehringer Ingelheim Investigational Site	Liepaja		Latvia
100	1264.3.37106 Boehringer Ingelheim Investigational Site	Ogre		Latvia
101	1264.3.37104 Boehringer Ingelheim Investigational Site	Riga		Latvia
102	1264.3.37108 Boehringer Ingelheim Investigational Site	Riga		Latvia
103	1264.3.37109 Boehringer Ingelheim Investigational Site	Riga		Latvia
104	1264.3.37111 Boehringer Ingelheim Investigational Site	Riga		Latvia
105	1264.3.37107 Boehringer Ingelheim Investigational Site	Talsi		Latvia
106	1264.3.37102 Boehringer Ingelheim Investigational Site	Tukums		Latvia
107	1264.3.37103 Boehringer Ingelheim Investigational Site	Valmiera		Latvia
108	1264.3.34013 Boehringer Ingelheim Investigational Site	Badía del Vallès - Barcelona		Spain
109	1264.3.34001 Boehringer Ingelheim Investigational Site	Barcelona		Spain
110	1264.3.34008 Boehringer Ingelheim Investigational Site	Barcelona		Spain
111	1264.3.34005 Boehringer Ingelheim Investigational Site	Borges del Camp- Tarragona		Spain
112	1264.3.34006 Boehringer Ingelheim Investigational Site	Canet de Mar - Barcelona		Spain
113	1264.3.34010 Boehringer Ingelheim Investigational Site	Centelles - Barcelona		Spain
114	1264.3.34004 Boehringer Ingelheim Investigational Site	L'Hospitalet de Llobregat - Barcelona		Spain
115	1264.3.34009 Boehringer Ingelheim Investigational Site	L'Hospitalet de Llobregat		Spain
116	1264.3.34002 Boehringer Ingelheim Investigational Site	Sant Adrià del Besós- Barcelona		Spain
117	1264.3.34007 Boehringer Ingelheim Investigational Site	Tarrega - Lleida		Spain
118	1264.3.34012 Boehringer Ingelheim Investigational Site	Valencia		Spain
119	1264.3.34011 Boehringer Ingelheim Investigational Site	Vic - Barcelona		Spain
120	1264.3.44032 Boehringer Ingelheim Investigational Site	Annan		United Kingdom
121	1264.3.44028 Boehringer Ingelheim Investigational Site	Ash Vale, Aldershot		United Kingdom
122	1264.3.44029 Boehringer Ingelheim Investigational Site	Baillieston, Glasgow		United Kingdom
123	1264.3.44008 Boehringer Ingelheim Investigational Site	Balham		United Kingdom
124	1264.3.44021 Boehringer Ingelheim Investigational Site	Bradford on Avon		United Kingdom
125	1264.3.44019 Boehringer Ingelheim Investigational Site	Burbage		United Kingdom
126	1264.3.44012 Boehringer Ingelheim Investigational Site	Chesterfield		United Kingdom
127	1264.3.44027 Boehringer Ingelheim Investigational Site	Chestfield, Whitstable		United Kingdom
128	1264.3.44011 Boehringer Ingelheim Investigational Site	Chippenham		United Kingdom
129	1264.3.44033 Boehringer Ingelheim Investigational Site	Johnstone		United Kingdom
130	1264.3.44007 Boehringer Ingelheim Investigational Site	Midsomer Norton		United Kingdom
131	1264.3.44034 Boehringer Ingelheim Investigational Site	Paisley		United Kingdom
132	1264.3.44031 Boehringer Ingelheim Investigational Site	Warminster		United Kingdom

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:

NCT01183013

Other Study ID Numbers:

1264.3
2008-008127-15

First Posted:

Aug 17, 2010

Last Update Posted:

Oct 20, 2014

Last Verified:

Oct 1, 2014

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2

Pioglitazone

Linagliptin

Study Results

Participant Flow

Recruitment Details	After Amendment #5, patients were considered COMPLETED at the end of Part A (30 weeks) or after their next Part B visit (up to 54 weeks) if already in Part B. Before Amendment #5, all patients were considered COMPLETED at the end of Part A + Part B (84 weeks).
Pre-assignment Detail

Arm/Group Title	Pio15/Pio30	Pio30/Pio30	Pio45/Pio45	Lina5/Lina5	Lina5Pio15/Lina5Pio30	Lina5Pio30/Lina5Pio30	Lina5Pio45/Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg for 30 weeks followed by pioglitazone 30mg for up to 54 weeks.	Participants treated with pioglitazone 30mg for 30 weeks followed by pioglitazone 30mg for up to 54 weeks.	Participants treated with pioglitazone 30 mg for 6 weeks and then were titrated up to pioglitazone 45mg for 24 weeks followed by pioglitazone 45mg for up to 54 weeks.	Participants treated with linagliptin 5mg once daily for 30 weeks followed by linagliptin 5mg once daily for up to 54 weeks.	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for 30 weeks followed by linagliptin 5mg + pioglitazone 30mg FDC for up to 54 weeks.	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for 30 weeks followed by linagliptin 5mg + pioglitazone 30mg FDC for up to 54 weeks.	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for 6 weeks and linagliptin 5mg + pioglitazone 45mg FDC for 24 weeks followed by linagliptin 5mg + pioglitazone 45mg FDC for up to 54 weeks.
Period Title: Overall Study
STARTED	131	140	138	135	126	133	133
COMPLETED	86	101	97	105	90	88	96
NOT COMPLETED	45	39	41	30	36	45	37

Baseline Characteristics

Arm/Group Title	Pio15/Pio30	Pio30/Pio30	Pio45/Pio45	Lina5/Lina5	Lina5Pio15/Lina5Pio30	Lina5Pio30/Lina5Pio30	Lina5Pio45/Lina5Pio45	Total
Arm/Group Description	Participants treated with pioglitazone 15mg for 30 weeks followed by pioglitazone 30mg for up to 54 weeks.	Participants treated with pioglitazone 30mg for 30 weeks followed by pioglitazone 30mg for up to 54 weeks.	Participants treated with pioglitazone 30 mg for 6 weeks and then were titrated up to pioglitazone 45mg for 24 weeks followed by pioglitazone 45mg for up to 54 weeks.	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for 30 weeks followed by linagliptin 5mg + pioglitazone 30mg FDC for up to 54 weeks.	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for 30 weeks followed by a blinded trial period on linagliptin 5mg + pioglitazone 30mg FDC	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for 30 weeks followed by linagliptin 5mg + pioglitazone 30mg FDC for up to 54 weeks.	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for 6 weeks and linagliptin 5mg + pioglitazone 45mg FDC for 24 weeks followed by linagliptin 5mg + pioglitazone 45mg FDC for up to 54 weeks.	Total of all reporting groups
Overall Participants	124	134	134	130	120	125	126	893
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.4 (10.4)	57.2 (11.1)	56.5 (11.1)	56.3 (10.1)	57.1 (10.2)	56.4 (10.0)	60.1 (10.2)	57.1 (10.5)
Sex: Female, Male (Count of Participants)
Female	57 46%	64 47.8%	66 49.3%	51 39.2%	54 45%	61 48.8%	57 45.2%	410 45.9%
Male	67 54%	70 52.2%	68 50.7%	79 60.8%	66 55%	64 51.2%	69 54.8%	483 54.1%
Baseline HbA1c (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	8.33 (0.93)	7.99 (0.85)	8.12 (0.87)	8.01 (0.88)	8.13 (0.94)	8.17 (1.07)	8.01 (0.81)	8.11 (0.91)
Baseline fasting plasma glucose (FPG) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	171.3 (39.3)	165.8 (40.0)	167.5 (37.9)	161.4 (38.1)	167.3 (39.5)	168.8 (46.8)	162.3 (36.8)	166.3 (39.9)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in HbA1c After 30 Weeks of Treatment.
Description	HbA1c is measured as a percentage. The change from baseline is the Week 30 HbA1c minus the baseline HbA1c.
Time Frame	Baseline and 30 weeks

Outcome Measure Data

Analysis Population Description
Patients from Full Analysis Set (FAS) with last observation carried forward (LOCF) used to handle missing values at Week 30. FAS is the patient set which includes all patients who were documented to have taken at least one dose of treatment and who had a baseline HbA1c value at at least one on-treatment HbA1c.

Arm/Group Title	Pio15	Pio30	Pio45	Lina5	Lina5Pio15	Lina5Pio30	Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for 6 weeks and were titrated to pioglitazone 45mg monotherapy for the next 24 weeks.	Participants treated with linagliptin 5mg once daily for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 6 weeks and were titrated to linagliptin 5mg + pioglitazone 45mg for the next 24 weeks.
Measure Participants	124	134	134	130	120	125	126
Mean (Standard Error) [percent]	-0.66 (0.09)	-0.69 (0.09)	-0.87 (0.09)	-0.39 (0.09)	-0.83 (0.09)	-1.06 (0.09)	-1.28 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pio15, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1571
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, prior anti-diabetic medication and country.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.17
	Confidence Interval	() 95% -0.41 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pio30, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95% -0.60 to -0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pio45, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.41
	Confidence Interval	(2-Sided) 95% -0.64 to -0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 95% -0.67 to -0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 95% -0.91 to -0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95% -1.12 to -0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 7.0% After 30 Weeks of Treatment
Description	Glycosylated hemoglobin is reported as a percentage of the total hemoglobin.
Time Frame	Baseline and 30 weeks

Outcome Measure Data

Analysis Population Description
FAS patients who also had baseline HbA1c>=7%.Non-completers (patients without a value at Week 30) were considered as failures (NCF).

Arm/Group Title	Pio15	Pio30	Pio45	Lina5	Lina5Pio15	Lina5Pio30	Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for 6 weeks and were titrated to pioglitazone 45mg monotherapy for the next 24 weeks	Participants treated with linagliptin 5mg once daily for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 6 weeks and were titrated to linagliptin 5mg + pioglitazone 45mg for the next 24 weeks.
Measure Participants	121	125	129	124	112	118	121
Number [participants]	39 31.5%	55 41%	68 50.7%	29 22.3%	45 37.5%	61 48.8%	81 64.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pio15, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4639
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.246
	Confidence Interval	() 95% 0.692 to 2.242
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pio30, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0546
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.746
	Confidence Interval	() 95% 0.989 to 3.083
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pio45, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0254
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.903
	Confidence Interval	() 95% 1.083 to 3.345
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.804
	Confidence Interval	() 95% 1.524 to 5.159
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.429
	Confidence Interval	() 95% 2.947 to 10.001
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	9.614
	Confidence Interval	() 95% 5.187 to 17.821
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 6.5% After 30 Weeks of Treatment
Description	Glycosylated hemoglobin is reported as a percentage of the total hemoglobin.
Time Frame	Baseline and 30 weeks

Outcome Measure Data

Analysis Population Description
FAS patients who also had baseline HbA1c >=6.5%. Non-completers (patients without a value at Week 30) were considered as failures (NCF)

Arm/Group Title	Pio15	Pio30	Pio45	Lina5	Lina5Pio15	Lina5Pio30	Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for 6 weeks and were titrated to pioglitazone 45mg monotherapy for the next 24 weeks	Participants treated with linagliptin 5mg once daily for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 6 weeks and were titrated to linagliptin 5mg + pioglitazone 45mg for the next 24 weeks.
Measure Participants	124	132	134	129	120	123	125
Number [participants]	20 16.1%	28 20.9%	39 29.1%	14 10.8%	24 20%	38 30.4%	43 34.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pio15, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7359
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.126
	Confidence Interval	() 95% 0.565 to 2.243
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pio30, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0363
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.905
	Confidence Interval	() 95% 1.042 to 3.484
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pio45, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4039
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.269
	Confidence Interval	() 95% 0.726 to 2.217
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0345
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.220
	Confidence Interval	() 95% 1.060 to 4.649
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.580
	Confidence Interval	() 95% 2.263 to 9.266
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.066
	Confidence Interval	() 95% 2.530 to 10.145
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 30 Weeks of Treatment)
Description	Glycosylated hemoglobin is reported as a percentage of the total hemoglobin.
Time Frame	Baseline and 30 weeks

Outcome Measure Data

Analysis Population Description
FAS with non-completers (without a value at Week 30) considered as failure

Arm/Group Title	Pio15	Pio30	Pio45	Lina5	Lina5Pio15	Lina5Pio30	Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for 6 weeks and were titrated to pioglitazone 45mg monotherapy for the next 24 weeks.	Participants treated with linagliptin 5mg once daily for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 6 weeks and were titrated to linagliptin 5mg + pioglitazone 45mg for the next 24 weeks.
Measure Participants	124	134	134	130	120	125	126
Number [participants]	79 63.7%	83 61.9%	90 67.2%	54 41.5%	79 65.8%	91 72.8%	107 84.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pio15, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7540
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.090
	Confidence Interval	() 95% 0.637 to 1.863
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pio30, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0506
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.707
	Confidence Interval	() 95% 0.999 to 2.918
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pio45, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.966
	Confidence Interval	(2-Sided) 95% 1.604 to 5.485
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.696
	Confidence Interval	() 95% 1.594 to 4.559
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.017
	Confidence Interval	() 95% 2.348 to 6.873
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	8.521
	Confidence Interval	() 95% 4.630 to 15.681
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	HbA1c Change From Baseline by Visit Over Time
Description	HbA1c is measured as a percentage. The change from baseline is the HbA1c over time minus the baseline HbA1c. The model includes fixed effects for treatment, continuous baseline HbA1c, prior andi-diabetic medication, country, visit and treatment. by visit interaction.
Time Frame	Baseline, week 6, week 12, week 18, week 24, week 30

Outcome Measure Data

Analysis Population Description
FAS (observed cases)

Arm/Group Title	Pio15	Pio30	Pio45	Lina5	Lina5Pio15	Lina5Pio30	Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for 6 weeks and were titrated to pioglitazone 45mg monotherapy for the next 24 weeks.	Participants treated with linagliptin 5mg once daily for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 6 weeks and were titrated to linagliptin 5mg + pioglitazone 45mg for the next 24 weeks.
Measure Participants	124	134	134	130	120	125	126
Change to week 6 (N=121,133,133,130,119,124,125)	-0.22 (0.06)	-0.16 (0.06)	-0.20 (0.06)	-0.23 (0.06)	-0.43 (0.06)	-0.47 (0.06)	-0.62 (0.06)
Change to week 12 (N=112,124,127,122,111,117,120)	-0.47 (0.08)	-0.43 (0.07)	-0.59 (0.07)	-0.36 (0.08)	-0.71 (0.08)	-0.92 (0.08)	-1.01 (0.08)
Change to week 18 (N=101,121,122,112,104,104,115)	-0.63 (0.09)	-0.58 (0.08)	-0.82 (0.08)	-0.39 (0.08)	-0.81 (0.09)	-1.07 (0.09)	-1.22 (0.09)
Change to week 24 (N=91,108,110,95,92,96,109)	-0.75 (0.09)	-0.67 (0.09)	-0.87 (0.09)	-0.39 (0.09)	-0.84 (0.09)	-1.10 (0.09)	-1.23 (0.09)
Change to week 30 (N=78,93,91,79,86,87,97)	-0.77 (0.09)	-0.73 (0.08)	-0.94 (0.09)	-0.37 (0.09)	-0.87 (0.09)	-1.09 (0.09)	-1.27 (0.09)

6. Secondary Outcome

Title	Fasting Plasma Glucose (FPG) Change From Baseline After 30 Weeks of Treatment
Description	The change from baseline is the FPG after 30 weeks minus the baseline FPG.
Time Frame	Baseline and 30 weeks

Outcome Measure Data

Analysis Population Description
Patients from Full Analysis Set (FAS) with a value for FPG at baseline and on-treatment. Last observation carried forward (LOCF) used to handle missing values at Week 30.

Arm/Group Title	Pio15	Pio30	Pio45	Lina5	Lina5Pio15	Lina5Pio30	Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for 6 weeks and were titrated to pioglitazone 45mg monotherapy for the next 24 weeks.	Participants treated with linagliptin 5mg once daily for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 6 weeks and were titrated to linagliptin 5mg + pioglitazone 45mg for the next 24 weeks.
Measure Participants	123	133	134	130	119	123	125
Mean (Standard Error) [mg/dL]	-15.16 (3.49)	-25.49 (3.28)	-28.69 (3.29)	-1.46 (3.35)	-18.84 (3.47)	-27.33 (3.46)	-35.19 (3.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pio15, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4275
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, continuous baseline FPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.68
	Confidence Interval	(2-Sided) 95% -12.77 to 5.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pio30, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6839
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, continuous baseline FPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.84
	Confidence Interval	(2-Sided) 95% -10.69 to 7.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pio45, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1466
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, continuous baseline FPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.50
	Confidence Interval	(2-Sided) 95% -15.29 to 2.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, continuous baseline FPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-17.38
	Confidence Interval	(2-Sided) 95% -26.35 to -8.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, continuous baseline FPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-25.87
	Confidence Interval	(2-Sided) 95% -34.77 to -16.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c, continuous baseline FPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-33.73
	Confidence Interval	(2-Sided) 95% -42.57 to -24.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Fasting Plasma Glucose (FPG) Change From Baseline by Visit Over Time
Description	The change from baseline is the FPG over time minus the baseline FPG. Model includes fixed effects for treatment, continuous baseline FPG, continuous baseline HbA1c, prior anti-diabetic medication, country, visit and treatment by visit interaction
Time Frame	Baseline, week 6, week 12, week 18, week 24, week 30

Outcome Measure Data

Analysis Population Description
FAS (observed cases)

Arm/Group Title	Pio15	Pio30	Pio45	Lina5	Lina5Pio15	Lina5Pio30	Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for 6 weeks and were titrated to pioglitazone 45mg monotherapy for the next 24 weeks.	Participants treated with linagliptin 5mg once daily for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 6 weeks and were titrated to linagliptin 5mg + pioglitazone 45mg for the next 24 weeks.
Measure Participants	124	134	134	130	120	125	126
Change at week 6 (N=118,132,133,130,119,122,124)	-14.43 (2.99)	-16.38 (2.80)	-15.72 (2.81)	-4.25 (2.84)	-19.25 (2.96)	-26.89 (2.94)	-28.36 (2.89)
Change at week 12 (N=111,124,126,122,108,114,118)	-10.63 (3.24)	-21.36 (3.04)	-25.30 (3.03)	-7.43 (3.08)	-17.99 (3.24)	-31.25 (3.19)	-28.53 (3.13)
Change at week 18 (N=100,122,121,111,104,103,114)	-16.68 (3.29)	-20.69 (3.02)	-28.68 (3.03)	-7.06 (3.13)	-19.01 (3.24)	-31.22 (3.25)	-30.66 (3.12)
Change at week 24 (N=90,108,108,96,93,93,108)	-16.25 (3.25)	-21.57 (2.99)	-27.67 (3.00)	-4.60 (3.13)	-16.68 (3.20)	-31.48 (3.20)	-31.49 (3.03)
Change at week 30 (N=76,91,89,79,82,87,98)	-17.66 (3.35)	-26.09 (3.08)	-31.76 (3.11)	-0.09 (3.24)	-17.93 (3.27)	-27.11 (3.22)	-34.04 (3.07)

8. Secondary Outcome

Title	Two-hour Postprandial Glucose (2hPPG) Change From Baseline at Week 30 by Meal Tolerance Test (MTT)
Description	The change from baseline is the 2hPPG after 30 weeks minus the baseline 2hPPG.
Time Frame	Baseline and 30 weeks

Outcome Measure Data

Analysis Population Description
MTT set: This patient set includes those patients in the FAS who had a valid MTT at baseline and at least one valid on-treatment MTT. An MTT is considered valid if both an FPG and a 2-hour PPG value are available.

Arm/Group Title	Pio15	Pio30	Pio45	Lina5	Lina5Pio15	Lina5Pio30	Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for 6 weeks and were titrated to pioglitazone 45mg monotherapy for the next 24 weeks.	Participants treated with linagliptin 5mg once daily for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 6 weeks and were titrated to linagliptin 5mg + pioglitazone 45mg for the next 24 weeks.
Measure Participants	29	34	25	22	28	26	31
Least Squares Mean (Standard Error) [mg/dL]	-30.65 (10.93)	-83.00 (9.85)	-82.98 (10.92)	-51.61 (11.67)	-67.26 (11.15)	-87.94 (11.14)	-84.77 (10.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pio15, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0057
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c and 2-hour PPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-36.61
	Confidence Interval	(2-Sided) 95% -62.42 to -10.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pio30, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7021
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c and 2-hour PPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.94
	Confidence Interval	() 95% -30.39 to 20.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pio45, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8932
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c and 2-hour PPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.78
	Confidence Interval	(2-Sided) 95% -27.95 to 24.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2706
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c and 2-hour PPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15.65
	Confidence Interval	(2-Sided) 95% -43.60 to 12.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0126
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c and 2-hour PPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-36.33
	Confidence Interval	(2-Sided) 95% -64.78 to -7.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0167
	Comments
	Method	ANCOVA
	Comments	The model includes fixed effects for treatment, continuous baseline HbA1c and 2-hour PPG, prior anti-diabetic medication and country.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-33.16
	Confidence Interval	(2-Sided) 95% -60.23 to -6.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Time to First Use of Rescue Therapy
Description	Proportion of patients at 30 weeks with rescue therapy using Kaplan-Meier analysis.
Time Frame	30 weeks

Outcome Measure Data

Analysis Population Description
FAS

Arm/Group Title	Pio15	Pio30	Pio45	Lina5	Lina5Pio15	Lina5Pio30	Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for 6 weeks and were titrated to pioglitazone 45mg monotherapy for the next 24 weeks.	Participants treated with linagliptin 5mg once daily for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 6 weeks and were titrated to linagliptin 5mg + pioglitazone 45mg for the next 24 weeks.
Measure Participants	124	134	134	130	120	125	126
Proportion event-free	0.8117 (50.5) 0.7%	0.8533 (47.8) 0.6%	0.9051 (55.3) 0.7%	0.7756 (47.7) 0.6%	0.8854 (61.5) 0.7%	0.9078 (54.7) 0.7%	0.9548 (65.7) 0.8%
Standard Error	0.0382 0%	0.0330 0%	0.0273 0%	0.0390 0%	0.0313 0%	0.0279 0%	0.0198 0%

10. Secondary Outcome

Title	Incidence of Rescue Therapy During the First 30 Weeks of Treatment
Description	Rescue therapy was defined to include any new antidiabetic medication taken for hyperglycemia and introduced on or after the start date of study treatment and before the end date of study treatment.
Time Frame	30 weeks

Outcome Measure Data

Analysis Population Description
FAS

Arm/Group Title	Pio15	Pio30	Pio45	Lina5	Lina5Pio15	Lina5Pio30	Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for the first 30 weeks	Participants treated with pioglitazone 30mg monotherapy for 6 weeks and were titrated to pioglitazone 45mg monotherapy for the next 24 weeks.	Participants treated with linagliptin 5mg once daily for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 30 weeks	Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for the first 6 weeks and were titrated to linagliptin 5mg + pioglitazone 45mg for the next 24 weeks.
Measure Participants	124	134	134	130	120	125	126
Number [participants]	20 16.1%	17 12.7%	11 8.2%	26 20%	12 10%	10 8%	5 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pio15, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3052
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.649
	Confidence Interval	() 95% 0.284 to 1.482
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pio30, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0844
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.456
	Confidence Interval	(2-Sided) 95% 0.187 to 1.112
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pio45, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1561
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.443
	Confidence Interval	(2-Sided) 95% 0.143 to 1.365
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio15
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0146
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.368
	Confidence Interval	() 95% 0.165 to 0.821
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio30
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.238
	Confidence Interval	() 95% 0.102 to 0.557
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lina5, Lina5Pio45
	Comments	Treatment comparisons are for fixed dose combination versus monotherapy.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Regression, Logistic
	Comments	A logistic regression model with terms for treatment, continuous HbA1c baseline, prior use of antidiabetic agents and country.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.141
	Confidence Interval	() 95% 0.050 to 0.397
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

	Pio15/Pio30		Pio30/Pio30		Pio45/Pio45		Lina5/Lina5		Lina5Pio15/Lina5Pio30		Lina5Pio30/Lina5Pio30		Lina5Pio45/Lina5Pio45
Time Frame	Up to 85 weeks
Adverse Event Reporting Description

Arm/Group Title	Pio15/Pio30		Pio30/Pio30		Pio45/Pio45		Lina5/Lina5		Lina5Pio15/Lina5Pio30		Lina5Pio30/Lina5Pio30		Lina5Pio45/Lina5Pio45
Arm/Group Description	Participants treated with pioglitazone 15mg for 30 weeks followed by pioglitazone 30mg for up to 54 weeks.		Participants treated with pioglitazone 30mg for 30 weeks followed by pioglitazone 30mg for up to 54 weeks.		Participants treated with pioglitazone 30 mg for 6 weeks and then were titrated up to pioglitazone 45mg for 24 weeks followed by pioglitazone 45mg for up to 54 weeks.		Participants treated with linagliptin 5mg once daily for 30 weeks followed by linagliptin 5mg once daily for up to 54 weeks.		Participants treated with linagliptin 5mg + pioglitazone 15mg fixed dose combination (FDC) for 30 weeks followed by linagliptin 5mg + pioglitazone 30mg FDC for up to 54 weeks.		Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for 30 weeks followed by linagliptin 5mg + pioglitazone 30mg FDC for up to 54 weeks.		Participants treated with linagliptin 5mg + pioglitazone 30mg fixed dose combination (FDC) for 6 weeks and linagliptin 5mg + pioglitazone 45mg FDC for 24 weeks followed by linagliptin 5mg + pioglitazone 45mg FDC for up to 54 weeks.
All Cause Mortality
	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)
Serious Adverse Events
	Pio15/Pio30		Pio30/Pio30		Pio45/Pio45		Lina5/Lina5		Lina5Pio15/Lina5Pio30		Lina5Pio30/Lina5Pio30		Lina5Pio45/Lina5Pio45
	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	9/131 (6.9%)		9/140 (6.4%)		5/138 (3.6%)		9/135 (6.7%)		9/126 (7.1%)		15/133 (11.3%)		10/133 (7.5%)
Blood and lymphatic system disorders
Anaemia	0/131 (0%)		0/140 (0%)		1/138 (0.7%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Idiopathic thrombocytopenic purpura	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Iron deficiency anaemia	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Cardiac disorders
Acute myocardial infarction	0/131 (0%)		1/140 (0.7%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		2/133 (1.5%)		0/133 (0%)
Atrial fibrillation	0/131 (0%)		0/140 (0%)		1/138 (0.7%)		0/135 (0%)		1/126 (0.8%)		0/133 (0%)		1/133 (0.8%)
Cardiopulmonary failure	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Congestive cardiomyopathy	0/131 (0%)		1/140 (0.7%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Coronary artery disease	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Myocardial infarction	1/131 (0.8%)		1/140 (0.7%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Supraventricular tachycardia	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		1/126 (0.8%)		1/133 (0.8%)		0/133 (0%)
Tachycardia	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Congenital, familial and genetic disorders
Hydrocele	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Endocrine disorders
Basedow's disease	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		1/126 (0.8%)		0/133 (0%)		0/133 (0%)
Eye disorders
Retinal artery embolism	0/131 (0%)		1/140 (0.7%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		1/126 (0.8%)		0/133 (0%)		0/133 (0%)
Constipation	0/131 (0%)		1/140 (0.7%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Diarrhoea	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Diverticulum	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Gastric haemorrhage	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Gastric ulcer	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Gastroduodenitis	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		1/133 (0.8%)
Gastrointestinal haemorrhage	0/131 (0%)		1/140 (0.7%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Intestinal haemorrhage	1/131 (0.8%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Pancreatitis acute	1/131 (0.8%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Upper gastrointestinal haemorrhage	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Vomiting	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
General disorders
Chest pain	0/131 (0%)		0/140 (0%)		0/138 (0%)		2/135 (1.5%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Fatigue	0/131 (0%)		0/140 (0%)		1/138 (0.7%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Hepatobiliary disorders
Cholecystitis acute	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Cholestasis	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		1/126 (0.8%)		0/133 (0%)		0/133 (0%)
Jaundice	1/131 (0.8%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Infections and infestations
Appendicitis	0/131 (0%)		1/140 (0.7%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Bronchitis	1/131 (0.8%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Device related infection	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Diverticulitis	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		1/133 (0.8%)
Gastroenteritis	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Infection	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Pneumonia	1/131 (0.8%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		1/133 (0.8%)
Pneumonia legionella	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		1/133 (0.8%)
Pyelonephritis	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		1/126 (0.8%)		0/133 (0%)		0/133 (0%)
Injury, poisoning and procedural complications
Anaemia postoperative	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Craniocerebral injury	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Fall	0/131 (0%)		0/140 (0%)		1/138 (0.7%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Joint dislocation	0/131 (0%)		0/140 (0%)		1/138 (0.7%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Traumatic fracture	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		1/126 (0.8%)		0/133 (0%)		0/133 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		1/126 (0.8%)		0/133 (0%)		0/133 (0%)
Intervertebral disc degeneration	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Intervertebral disc protrusion	1/131 (0.8%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Lumbar spinal stenosis	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Rotator cuff syndrome	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		1/133 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/131 (0%)		1/140 (0.7%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Breast cancer	0/131 (0%)		0/140 (0%)		1/138 (0.7%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Chronic lymphocytic leukaemia	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Colon cancer	0/131 (0%)		0/140 (0%)		1/138 (0.7%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Hairy cell leukaemia	1/131 (0.8%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Pancreatic carcinoma stage II	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		1/126 (0.8%)		0/133 (0%)		0/133 (0%)
Rectosigmoid cancer	1/131 (0.8%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Renal cancer	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		1/133 (0.8%)
Renal cell carcinoma	0/131 (0%)		1/140 (0.7%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Small intestine carcinoma	1/131 (0.8%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Squamous cell carcinoma of skin	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Tumour invasion	0/131 (0%)		0/140 (0%)		1/138 (0.7%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Uterine leiomyoma	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		1/133 (0.8%)
Nervous system disorders
Carpal tunnel syndrome	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		1/126 (0.8%)		0/133 (0%)		0/133 (0%)
Encephalitis	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Peripheral nerve palsy	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Radiculopathy	0/131 (0%)		0/140 (0%)		1/138 (0.7%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Psychiatric disorders
Bipolar disorder	1/131 (0.8%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Depression	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		1/126 (0.8%)		0/133 (0%)		0/133 (0%)
Renal and urinary disorders
Renal colic	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Pleural effusion	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Pneumothorax	1/131 (0.8%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Pulmonary embolism	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Sleep apnoea syndrome	0/131 (0%)		1/140 (0.7%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Skin and subcutaneous tissue disorders
Skin necrosis	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		1/133 (0.8%)
Surgical and medical procedures
Gastric bypass	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		0/133 (0%)		1/133 (0.8%)
Hip arthroplasty	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Vascular graft	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Vascular disorders
Aortic stenosis	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Arteriovenous fistula	0/131 (0%)		0/140 (0%)		0/138 (0%)		1/135 (0.7%)		0/126 (0%)		0/133 (0%)		0/133 (0%)
Hypertensive crisis	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Peripheral ischaemia	0/131 (0%)		0/140 (0%)		0/138 (0%)		0/135 (0%)		0/126 (0%)		1/133 (0.8%)		0/133 (0%)
Other (Not Including Serious) Adverse Events
	Pio15/Pio30		Pio30/Pio30		Pio45/Pio45		Lina5/Lina5		Lina5Pio15/Lina5Pio30		Lina5Pio30/Lina5Pio30		Lina5Pio45/Lina5Pio45
	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	57/131 (43.5%)		55/140 (39.3%)		66/138 (47.8%)		57/135 (42.2%)		52/126 (41.3%)		58/133 (43.6%)		56/133 (42.1%)
Gastrointestinal disorders
Diarrhoea	2/131 (1.5%)		0/140 (0%)		5/138 (3.6%)		7/135 (5.2%)		10/126 (7.9%)		2/133 (1.5%)		3/133 (2.3%)
General disorders
Oedema	4/131 (3.1%)		1/140 (0.7%)		7/138 (5.1%)		0/135 (0%)		0/126 (0%)		12/133 (9%)		4/133 (3%)
Oedema peripheral	13/131 (9.9%)		11/140 (7.9%)		11/138 (8%)		6/135 (4.4%)		8/126 (6.3%)		9/133 (6.8%)		15/133 (11.3%)
Infections and infestations
Bronchitis	5/131 (3.8%)		4/140 (2.9%)		7/138 (5.1%)		4/135 (3%)		3/126 (2.4%)		2/133 (1.5%)		5/133 (3.8%)
Nasopharyngitis	9/131 (6.9%)		10/140 (7.1%)		4/138 (2.9%)		10/135 (7.4%)		9/126 (7.1%)		8/133 (6%)		3/133 (2.3%)
Upper respiratory tract infection	2/131 (1.5%)		6/140 (4.3%)		9/138 (6.5%)		5/135 (3.7%)		4/126 (3.2%)		6/133 (4.5%)		6/133 (4.5%)
Urinary tract infection	7/131 (5.3%)		7/140 (5%)		8/138 (5.8%)		8/135 (5.9%)		5/126 (4%)		7/133 (5.3%)		7/133 (5.3%)
Metabolism and nutrition disorders
Hyperglycaemia	9/131 (6.9%)		10/140 (7.1%)		5/138 (3.6%)		14/135 (10.4%)		8/126 (6.3%)		8/133 (6%)		5/133 (3.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/131 (2.3%)		5/140 (3.6%)		9/138 (6.5%)		7/135 (5.2%)		1/126 (0.8%)		4/133 (3%)		4/133 (3%)
Back pain	12/131 (9.2%)		5/140 (3.6%)		10/138 (7.2%)		6/135 (4.4%)		8/126 (6.3%)		7/133 (5.3%)		12/133 (9%)
Pain in extremity	5/131 (3.8%)		5/140 (3.6%)		5/138 (3.6%)		3/135 (2.2%)		7/126 (5.6%)		7/133 (5.3%)		6/133 (4.5%)
Nervous system disorders
Dizziness	0/131 (0%)		7/140 (5%)		3/138 (2.2%)		4/135 (3%)		4/126 (3.2%)		9/133 (6.8%)		4/133 (3%)
Headache	7/131 (5.3%)		7/140 (5%)		9/138 (6.5%)		6/135 (4.4%)		5/126 (4%)		5/133 (3.8%)		6/133 (4.5%)
Vascular disorders
Hypertension	12/131 (9.2%)		4/140 (2.9%)		7/138 (5.1%)		9/135 (6.7%)		6/126 (4.8%)		5/133 (3.8%)		1/133 (0.8%)

Limitations/Caveats

The study (Part B treatment only) was stopped early by protocol amendment #5, although Part A (time frame for all efficacy outcomes) proceeded to completion

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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.

Results Point of Contact

Name/Title	Boehringer Ingelheim Call Center
Organization	Boehringer Ingelheim Pharmaceuticals
Phone	1-800-243-0127
Email	clintriage.rdg@boehringer-ingelheim.com

Responsible Party:

Boehringer Ingelheim

ClinicalTrials.gov Identifier:

NCT01183013

Other Study ID Numbers:

1264.3
2008-008127-15

First Posted:

Aug 17, 2010

Last Update Posted:

Oct 20, 2014

Last Verified:

Oct 1, 2014

30 Week Parallel Group Comparison Study of Linagliptin + Pioglitazone (5+15, 5+30 and 5+45 mg) qd Versus Respective Monotherapies, Followed by a Comparison of 5mg+30mg and 5mg+45mg Versus Respective Monotherapies in Type 2 Diabetes for up to 54 Weeks

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion criteria:

Exclusion criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Additional Information:

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Statistical Analysis 6

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Statistical Analysis 6

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Statistical Analysis 6

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Statistical Analysis 6

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Statistical Analysis 6

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Statistical Analysis 6

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Statistical Analysis 6

Adverse Events

All Cause Mortality

Serious Adverse Events