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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

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ClinicalTrials.gov Identifier: NCT01183013
Recruitment Status : Completed
First Posted : August 17, 2010
Results First Posted : April 21, 2014
Last Update Posted : October 20, 2014
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions 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
Enrollment 936
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 Details  
Arm/Group Title Pio15/Pio30 Pio30/Pio30 Pio45/Pio45 Lina5/Lina5 Lina5Pio15/Lina5Pio30 Lina5Pio30/Lina5Pio30 Lina5Pio45/Lina5Pio45
Hide 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 [1] 101 [1] 97 [1] 105 [1] 90 [1] 88 [1] 96 [1]
Not Completed 45 39 41 30 36 45 37
Reason Not Completed
Adverse Event             6             8             5             5             10             10             6
Lack of Efficacy             3             2             1             2             1             2             0
Protocol Violation             5             2             4             0             4             3             3
Lost to Follow-up             7             3             4             3             2             6             5
Withdrawal by Subject             9             13             10             8             7             9             10
Reasons other than stated above             15             11             17             12             12             15             13
[1]
Completed is first 30 weeks (Part A) or up to 84 weeks in relation to Protocol Amendment #5
Arm/Group Title Pio15/Pio30 Pio30/Pio30 Pio45/Pio45 Lina5/Lina5 Lina5Pio15/Lina5Pio30 Lina5Pio30/Lina5Pio30 Lina5Pio45/Lina5Pio45 Total
Hide 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 Number of Baseline Participants 124 134 134 130 120 125 126 893
Hide Baseline Analysis Population Description
All patients from the Full Analysis Set (FAS) which includes those patients in the treated set who had a baseline HbA1c value and at least one on-treatment HbA1c value.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 124 participants 134 participants 134 participants 130 participants 120 participants 125 participants 126 participants 893 participants
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 124 participants 134 participants 134 participants 130 participants 120 participants 125 participants 126 participants 893 participants
Female
57
  46.0%
64
  47.8%
66
  49.3%
51
  39.2%
54
  45.0%
61
  48.8%
57
  45.2%
410
  45.9%
Male
67
  54.0%
70
  52.2%
68
  50.7%
79
  60.8%
66
  55.0%
64
  51.2%
69
  54.8%
483
  54.1%
Baseline HbA1c  
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 124 participants 134 participants 134 participants 130 participants 120 participants 125 participants 126 participants 893 participants
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)  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 124 participants 134 participants 134 participants 130 participants 120 participants 125 participants 126 participants 893 participants
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)
1.Primary Outcome
Title Change From Baseline in HbA1c After 30 Weeks of Treatment.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 124 134 134 130 120 125 126
Mean (Standard Error)
Unit of Measure: 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)
Show Statistical Analysis 1 Hide 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 [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.17
Confidence Interval 95%
-0.41 to 0.07
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 7.0% After 30 Weeks of Treatment
Hide Description Glycosylated hemoglobin is reported as a percentage of the total hemoglobin.
Time Frame Baseline and 30 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 121 125 129 124 112 118 121
Measure Type: Number
Unit of Measure: participants
39 55 68 29 45 61 81
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.4639
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0546
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0254
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 6.5% After 30 Weeks of Treatment
Hide Description Glycosylated hemoglobin is reported as a percentage of the total hemoglobin.
Time Frame Baseline and 30 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 124 132 134 129 120 123 125
Measure Type: Number
Unit of Measure: participants
20 28 39 14 24 38 43
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.7359
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0363
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.4039
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0345
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 30 Weeks of Treatment)
Hide Description Glycosylated hemoglobin is reported as a percentage of the total hemoglobin.
Time Frame Baseline and 30 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 124 134 134 130 120 125 126
Measure Type: Number
Unit of Measure: participants
79 83 90 54 79 91 107
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.7540
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0506
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
5.Secondary Outcome
Title HbA1c Change From Baseline by Visit Over Time
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS (observed cases)
Arm/Group Title Pio15 Pio30 Pio45 Lina5 Lina5Pio15 Lina5Pio30 Lina5Pio45
Hide 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.
Overall Number of Participants Analyzed 124 134 134 130 120 125 126
Mean (Standard Error)
Unit of Measure: percent
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
Hide Description The change from baseline is the FPG after 30 weeks minus the baseline FPG.
Time Frame Baseline and 30 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 123 133 134 130 119 123 125
Mean (Standard Error)
Unit of Measure: 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)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.4275
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.6839
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.1466
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Fasting Plasma Glucose (FPG) Change From Baseline by Visit Over Time
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS (observed cases)
Arm/Group Title Pio15 Pio30 Pio45 Lina5 Lina5Pio15 Lina5Pio30 Lina5Pio45
Hide 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.
Overall Number of Participants Analyzed 124 134 134 130 120 125 126
Mean (Standard Error)
Unit of Measure: mg/dL
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)
Hide Description The change from baseline is the 2hPPG after 30 weeks minus the baseline 2hPPG.
Time Frame Baseline and 30 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 29 34 25 22 28 26 31
Least Squares Mean (Standard Error)
Unit of Measure: 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)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0057
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.7021
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.8932
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.2706
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0126
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0167
Comments [Not Specified]
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
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time to First Use of Rescue Therapy
Hide Description Proportion of patients at 30 weeks with rescue therapy using Kaplan-Meier analysis.
Time Frame 30 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Pio15 Pio30 Pio45 Lina5 Lina5Pio15 Lina5Pio30 Lina5Pio45
Hide 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.
Overall Number of Participants Analyzed 124 134 134 130 120 125 126
Measure Type: Number
Unit of Measure: Proportion of participants
Proportion event-free 0.8117 0.8533 0.9051 0.7756 0.8854 0.9078 0.9548
Standard Error 0.0382 0.0330 0.0273 0.0390 0.0313 0.0279 0.0198
10.Secondary Outcome
Title Incidence of Rescue Therapy During the First 30 Weeks of Treatment
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Pio15 Pio30 Pio45 Lina5 Lina5Pio15 Lina5Pio30 Lina5Pio45
Hide 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.
Overall Number of Participants Analyzed 124 134 134 130 120 125 126
Measure Type: Number
Unit of Measure: participants
20 17 11 26 12 10 5
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.3052
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0844
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.1561
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0146
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
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
Estimation Comments [Not Specified]
Time Frame Up to 85 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pio15/Pio30 Pio30/Pio30 Pio45/Pio45 Lina5/Lina5 Lina5Pio15/Lina5Pio30 Lina5Pio30/Lina5Pio30 Lina5Pio45/Lina5Pio45
Hide 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
Pio15/Pio30 Pio30/Pio30 Pio45/Pio45 Lina5/Lina5 Lina5Pio15/Lina5Pio30 Lina5Pio30/Lina5Pio30 Lina5Pio45/Lina5Pio45
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Pio15/Pio30 Pio30/Pio30 Pio45/Pio45 Lina5/Lina5 Lina5Pio15/Lina5Pio30 Lina5Pio30/Lina5Pio30 Lina5Pio45/Lina5Pio45
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/131 (6.87%)   9/140 (6.43%)   5/138 (3.62%)   9/135 (6.67%)   9/126 (7.14%)   15/133 (11.28%)   10/133 (7.52%) 
Blood and lymphatic system disorders               
Anaemia  1  0/131 (0.00%)  0/140 (0.00%)  1/138 (0.72%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Idiopathic thrombocytopenic purpura  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Iron deficiency anaemia  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Cardiac disorders               
Acute myocardial infarction  1  0/131 (0.00%)  1/140 (0.71%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  2/133 (1.50%)  0/133 (0.00%) 
Atrial fibrillation  1  0/131 (0.00%)  0/140 (0.00%)  1/138 (0.72%)  0/135 (0.00%)  1/126 (0.79%)  0/133 (0.00%)  1/133 (0.75%) 
Cardiopulmonary failure  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Congestive cardiomyopathy  1  0/131 (0.00%)  1/140 (0.71%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Coronary artery disease  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Myocardial infarction  1  1/131 (0.76%)  1/140 (0.71%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Supraventricular tachycardia  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  1/126 (0.79%)  1/133 (0.75%)  0/133 (0.00%) 
Tachycardia  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Congenital, familial and genetic disorders               
Hydrocele  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Endocrine disorders               
Basedow's disease  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  1/126 (0.79%)  0/133 (0.00%)  0/133 (0.00%) 
Eye disorders               
Retinal artery embolism  1  0/131 (0.00%)  1/140 (0.71%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Gastrointestinal disorders               
Abdominal pain upper  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  1/126 (0.79%)  0/133 (0.00%)  0/133 (0.00%) 
Constipation  1  0/131 (0.00%)  1/140 (0.71%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Diarrhoea  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Diverticulum  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Gastric haemorrhage  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Gastric ulcer  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Gastroduodenitis  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  1/133 (0.75%) 
Gastrointestinal haemorrhage  1  0/131 (0.00%)  1/140 (0.71%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Intestinal haemorrhage  1  1/131 (0.76%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Pancreatitis acute  1  1/131 (0.76%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Upper gastrointestinal haemorrhage  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Vomiting  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
General disorders               
Chest pain  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  2/135 (1.48%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Fatigue  1  0/131 (0.00%)  0/140 (0.00%)  1/138 (0.72%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Hepatobiliary disorders               
Cholecystitis acute  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Cholestasis  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  1/126 (0.79%)  0/133 (0.00%)  0/133 (0.00%) 
Jaundice  1  1/131 (0.76%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Infections and infestations               
Appendicitis  1  0/131 (0.00%)  1/140 (0.71%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Bronchitis  1  1/131 (0.76%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Device related infection  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Diverticulitis  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  1/133 (0.75%) 
Gastroenteritis  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Infection  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Pneumonia  1  1/131 (0.76%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  1/133 (0.75%) 
Pneumonia legionella  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  1/133 (0.75%) 
Pyelonephritis  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  1/126 (0.79%)  0/133 (0.00%)  0/133 (0.00%) 
Injury, poisoning and procedural complications               
Anaemia postoperative  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Craniocerebral injury  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Fall  1  0/131 (0.00%)  0/140 (0.00%)  1/138 (0.72%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Joint dislocation  1  0/131 (0.00%)  0/140 (0.00%)  1/138 (0.72%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Traumatic fracture  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Metabolism and nutrition disorders               
Hypoglycaemia  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  1/126 (0.79%)  0/133 (0.00%)  0/133 (0.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  1/126 (0.79%)  0/133 (0.00%)  0/133 (0.00%) 
Intervertebral disc degeneration  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Intervertebral disc protrusion  1  1/131 (0.76%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Lumbar spinal stenosis  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Rotator cuff syndrome  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  1/133 (0.75%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Basal cell carcinoma  1  0/131 (0.00%)  1/140 (0.71%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Breast cancer  1  0/131 (0.00%)  0/140 (0.00%)  1/138 (0.72%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Chronic lymphocytic leukaemia  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Colon cancer  1  0/131 (0.00%)  0/140 (0.00%)  1/138 (0.72%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Hairy cell leukaemia  1  1/131 (0.76%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Pancreatic carcinoma stage II  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  1/126 (0.79%)  0/133 (0.00%)  0/133 (0.00%) 
Rectosigmoid cancer  1  1/131 (0.76%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Renal cancer  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  1/133 (0.75%) 
Renal cell carcinoma  1  0/131 (0.00%)  1/140 (0.71%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Small intestine carcinoma  1  1/131 (0.76%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Squamous cell carcinoma of skin  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Tumour invasion  1  0/131 (0.00%)  0/140 (0.00%)  1/138 (0.72%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Uterine leiomyoma  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  1/133 (0.75%) 
Nervous system disorders               
Carpal tunnel syndrome  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  1/126 (0.79%)  0/133 (0.00%)  0/133 (0.00%) 
Encephalitis  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Peripheral nerve palsy  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Radiculopathy  1  0/131 (0.00%)  0/140 (0.00%)  1/138 (0.72%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Psychiatric disorders               
Bipolar disorder  1  1/131 (0.76%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Depression  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  1/126 (0.79%)  0/133 (0.00%)  0/133 (0.00%) 
Renal and urinary disorders               
Renal colic  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Chronic obstructive pulmonary disease  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Pleural effusion  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Pneumothorax  1  1/131 (0.76%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Pulmonary embolism  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Sleep apnoea syndrome  1  0/131 (0.00%)  1/140 (0.71%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Skin and subcutaneous tissue disorders               
Skin necrosis  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  1/133 (0.75%) 
Surgical and medical procedures               
Gastric bypass  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  0/133 (0.00%)  1/133 (0.75%) 
Hip arthroplasty  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Vascular graft  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Vascular disorders               
Aortic stenosis  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Arteriovenous fistula  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  1/135 (0.74%)  0/126 (0.00%)  0/133 (0.00%)  0/133 (0.00%) 
Hypertensive crisis  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Peripheral ischaemia  1  0/131 (0.00%)  0/140 (0.00%)  0/138 (0.00%)  0/135 (0.00%)  0/126 (0.00%)  1/133 (0.75%)  0/133 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pio15/Pio30 Pio30/Pio30 Pio45/Pio45 Lina5/Lina5 Lina5Pio15/Lina5Pio30 Lina5Pio30/Lina5Pio30 Lina5Pio45/Lina5Pio45
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   57/131 (43.51%)   55/140 (39.29%)   66/138 (47.83%)   57/135 (42.22%)   52/126 (41.27%)   58/133 (43.61%)   56/133 (42.11%) 
Gastrointestinal disorders               
Diarrhoea  1  2/131 (1.53%)  0/140 (0.00%)  5/138 (3.62%)  7/135 (5.19%)  10/126 (7.94%)  2/133 (1.50%)  3/133 (2.26%) 
General disorders               
Oedema  1  4/131 (3.05%)  1/140 (0.71%)  7/138 (5.07%)  0/135 (0.00%)  0/126 (0.00%)  12/133 (9.02%)  4/133 (3.01%) 
Oedema peripheral  1  13/131 (9.92%)  11/140 (7.86%)  11/138 (7.97%)  6/135 (4.44%)  8/126 (6.35%)  9/133 (6.77%)  15/133 (11.28%) 
Infections and infestations               
Bronchitis  1  5/131 (3.82%)  4/140 (2.86%)  7/138 (5.07%)  4/135 (2.96%)  3/126 (2.38%)  2/133 (1.50%)  5/133 (3.76%) 
Nasopharyngitis  1  9/131 (6.87%)  10/140 (7.14%)  4/138 (2.90%)  10/135 (7.41%)  9/126 (7.14%)  8/133 (6.02%)  3/133 (2.26%) 
Upper respiratory tract infection  1  2/131 (1.53%)  6/140 (4.29%)  9/138 (6.52%)  5/135 (3.70%)  4/126 (3.17%)  6/133 (4.51%)  6/133 (4.51%) 
Urinary tract infection  1  7/131 (5.34%)  7/140 (5.00%)  8/138 (5.80%)  8/135 (5.93%)  5/126 (3.97%)  7/133 (5.26%)  7/133 (5.26%) 
Metabolism and nutrition disorders               
Hyperglycaemia  1  9/131 (6.87%)  10/140 (7.14%)  5/138 (3.62%)  14/135 (10.37%)  8/126 (6.35%)  8/133 (6.02%)  5/133 (3.76%) 
Musculoskeletal and connective tissue disorders               
Arthralgia  1  3/131 (2.29%)  5/140 (3.57%)  9/138 (6.52%)  7/135 (5.19%)  1/126 (0.79%)  4/133 (3.01%)  4/133 (3.01%) 
Back pain  1  12/131 (9.16%)  5/140 (3.57%)  10/138 (7.25%)  6/135 (4.44%)  8/126 (6.35%)  7/133 (5.26%)  12/133 (9.02%) 
Pain in extremity  1  5/131 (3.82%)  5/140 (3.57%)  5/138 (3.62%)  3/135 (2.22%)  7/126 (5.56%)  7/133 (5.26%)  6/133 (4.51%) 
Nervous system disorders               
Dizziness  1  0/131 (0.00%)  7/140 (5.00%)  3/138 (2.17%)  4/135 (2.96%)  4/126 (3.17%)  9/133 (6.77%)  4/133 (3.01%) 
Headache  1  7/131 (5.34%)  7/140 (5.00%)  9/138 (6.52%)  6/135 (4.44%)  5/126 (3.97%)  5/133 (3.76%)  6/133 (4.51%) 
Vascular disorders               
Hypertension  1  12/131 (9.16%)  4/140 (2.86%)  7/138 (5.07%)  9/135 (6.67%)  6/126 (4.76%)  5/133 (3.76%)  1/133 (0.75%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 15.1
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
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01183013     History of Changes
Other Study ID Numbers: 1264.3
2008-008127-15 ( EudraCT Number: EudraCT )
First Submitted: August 16, 2010
First Posted: August 17, 2010
Results First Submitted: March 12, 2014
Results First Posted: April 21, 2014
Last Update Posted: October 20, 2014