Efficacy and Safety of B I1356 (Linagliptin) vs. Placebo Added to Metformin Background Therapy in Patients With Type 2 Diabetes

• ClinicalTrials.gov Identifier: NCT00601250
• Recruitment Status: Completed
• First Posted: January 28, 2008
• Results First Posted: June 7, 2011
• Last Update Posted: January 28, 2014
• Sponsor: Boehringer Ingelheim
• Information provided by: Boehringer Ingelheim

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 2
• Intervention: Drug: linagliptin
• Enrollment: 701

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Period Title: Overall Study
Started	177 [1]	523 [2]
Completed	163 [3]	484 [3]
Not Completed	14	39
Reason Not Completed
Adverse Event	3	9
Protocol Violation	3	2
Lost to Follow-up	2	6
Withdrawal by Subject	4	13
Other incl. lack of efficacy	2	9
[1] number who started treatment; [2] number who started treatment. One additional patient was randomised but not treated.; [3] number who completed treatment

Baseline Characteristics

Arm/Group Title		Placebo	Linagliptin	Total
Arm/Group Description		Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg	Total of all reporting groups
Overall Number of Baseline Participants		177	523	700
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	177 participants	523 participants	700 participants
		56.6 (10.9)	56.5 (10.1)	56.5 (10.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	177 participants	523 participants	700 participants
	Female	76 42.9%	245 46.8%	321 45.9%
	Male	101 57.1%	278 53.2%	379 54.1%
Body Mass Index (BMI) continuous; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	177 participants	523 participants	700 participants
		30.05 (5.01)	29.85 (4.84)	29.90 (4.88)
Glycosylated haemoglobin A1 (HbA1C); Mean (Standard Deviation); Unit of measure: Percent
	Number Analyzed	177 participants	523 participants	700 participants
		8.02 (0.88)	8.09 (0.86)	8.08 (0.87)
Fasting blood plasma glucose (FPG); Mean (Standard Deviation); Unit of measure: mg/dL
	Number Analyzed	177 participants	523 participants	700 participants
		166.42 (41.89)	169.62 (43.51)	168.81 (43.10)

Outcome Measures

1. Primary Outcome

Title	HbA1c Change From Baseline at Week 24
Description	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule.

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	175	513
Mean (Standard Error); Unit of Measure: Percent
	0.15 (0.06)	-0.49 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.64
	Confidence Interval	(2-Sided) 95%; -0.78 to -0.5
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.07
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	HbA1c Change From Baseline at Week 6
Description	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time Frame	Baseline and week 6

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule.

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	175	513
Mean (Standard Error); Unit of Measure: Percent
	0.069 (0.044)	-0.363 (0.027)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.431
	Confidence Interval	(2-Sided) 95%; -0.530 to -0.333
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.050
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	HbA1c Change From Baseline at Week 12
Description	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule.

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	175	513
Mean (Standard Error); Unit of Measure: Percent
	0.096 (0.056)	-0.499 (0.034)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.596
	Confidence Interval	95%; -0.721 to -0.471
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.064
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	HbA1c Change From Baseline at Week 18
Description	HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time Frame	Baseline and week 18

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all treated and randomised patients with a baseline and at least one on-treatment HbA1c measurement available. Last observation carried forward (LOCF) was used as the imputation rule.

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	175	513
Mean (Standard Error); Unit of Measure: Percent
	0.147 (0.061)	-0.502 (0.037)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.648
	Confidence Interval	95%; -0.785 to -0.512
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.069
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	FPG Change From Baseline at Week 24
Description	This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	159	495
Mean (Standard Error); Unit of Measure: mg/dL
	10.46 (2.80)	-10.68 (1.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-21.13
	Confidence Interval	95%; -27.3 to -14.96
	Parameter Dispersion	Type: Standard Error of the mean; Value: 3.14
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	FPG Change From Baseline at Week 6
Description	This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Time Frame	Baseline and week 6

Outcome Measure Data

Analysis Population Description

This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	159	495
Mean (Standard Error); Unit of Measure: mg/dL
	4.58 (2.38)	-11.94 (1.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-16.52
	Confidence Interval	95%; -21.76 to -11.29
	Parameter Dispersion	Type: Standard Error of the mean; Value: 2.67
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	FPG Change From Baseline at Week 12
Description	This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	159	495
Mean (Standard Error); Unit of Measure: mg/dL
	3.86 (2.60)	-12.86 (1.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-16.73
	Confidence Interval	95%; -22.44 to -11.01
	Parameter Dispersion	Type: Standard Error of the mean; Value: 2.91
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	FPG Change From Baseline at Week 18
Description	This change from baseline reflects the Week 18 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication.
Time Frame	Baseline and week 18

Outcome Measure Data

Analysis Population Description

This population includes the FAS using the LOCF imputation, with the further restriction of patients with a baseline and post-baseline FPG value.

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	159	495
Mean (Standard Error); Unit of Measure: mg/dL
	10.32 (2.72)	-10.51 (1.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-20.83
	Confidence Interval	95%; -26.81 to -14.84
	Parameter Dispersion	Type: Standard Error of the mean; Value: 3.05
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Percentage of Patients With HbA1c <7.0% at Week 24.
Description	The percentage of patients with an HbA1c value below 7.0% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c >= 7.0%. Only patients with baseline HbA1c >= 7%
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

This population includes the FAS with baseline HbA1c >= 7.0%. Non-completers were considered as failure imputation (NCF).

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	163	485
Measure Type: Number; Unit of Measure: percentage of patients
	9.2	26.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo The odds-ratio is based on a logistic regression model including baseline HbA1c and previous antidiabetic medication.
	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	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.395
	Confidence Interval	95%; 2.410 to 8.013
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Percentage of Patients With HbA1c < 7.0% at Week 24
Description	The percentage of patients with an HbA1c value below 7.0% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c >= 7.0%.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

This population includes the Full Analysis Set (FAS). Non-completers were considered as failure imputation (NCF).

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	175	513
Measure Type: Number; Unit of Measure: percentage of patients
	11.4	28.3

11. Secondary Outcome

Title	Percentage of Patients With HbA1c <6.5% at Week 24
Description	The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c >= 6.5%. Only patients with baseline HbA1c >= 6.5%
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

This population includes the FAS with baseline HbA1c >= 6.5%. Non-completers were considered as failure imputation (NCF).

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	171	511
Measure Type: Number; Unit of Measure: percentage of patients
	2.3	10.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo The odds-ratio is based on a logistic regression model including baseline HbA1c and previous antidiabetic medication.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0016
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.456
	Confidence Interval	95%; 1.907 to 15.614
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Percentage of Patients With HbA1c<6.5% at Week 24
Description	The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c >= 6.5%.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

This population includes the Full Analysis Set (FAS). Non-completers were considered as failure imputation (NCF).

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	175	513
Measure Type: Number; Unit of Measure: percentage of patients
	3.4	10.7

13. Secondary Outcome

Title	Percentage of Patients Who Have a HbA1c Lowering by 0.5% at Week 24
Description	The percentage of patients with an HbA1c reduction from baseline >= 0.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5%.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all patients with a baseline and at least one on treatment HbA1c measurement available. Non-completers were considered as failure imputation (NCF).

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	175	513
Measure Type: Number; Unit of Measure: percentage of patients
	21.7	49.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo The odds-ratio is based on a logistic regression model including baseline HbA1c and previous antidiabetic medication.
	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	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.754
	Confidence Interval	95%; 2.486 to 5.669
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Adjusted Means for 2h Post Prandial Blood Glucose (PPG) Change From Baseline at Week 24
Description	This change from baseline reflects the Week 24 2h PPG minus the baseline 2h PPG. Means are treatment adjusted for baseline HbA1c, baseline PPG and previous anti-diabetic medication.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

Meal Tolerance Test (MTT) set (treated and randomised patients with adequate MTT results available at the beginning and end of the randomised treatment period)

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	21	78
Mean (Standard Error); Unit of Measure: mg/dL
	18.27 (12.85)	-48.86 (7.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-67.13
	Confidence Interval	(2-Sided) 95%; -94.69 to -39.58
	Parameter Dispersion	Type: Standard Error of the mean; Value: 13.88
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	2 Hour Post-Prandial Glucose (PPG) Increment Over Fasting Plasma Glucose (FPG) at Week 24
Description	This change from baseline reflects the Week 24 (2h PPG - FPG) minus the baseline (2h PPG - FPG). Means are treatment adjusted for baseline HbA1c, baseline 2h PPG increment over FPG and previous anti-diabetic medication.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

Meal Tolerance Test (MTT) set (treated and randomised patients with adequate MTT results available at the beginning and end of the randomised treatment period)

Arm/Group Title	Placebo	Linagliptin
Arm/Group Description:	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
Overall Number of Participants Analyzed	21	74
Least Squares Mean (Standard Error); Unit of Measure: mg/dL
	10.90 (9.23)	-30.90 (5.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin
	Comments	Linagliptin vs. Placebo
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-41.80
	Confidence Interval	(2-Sided) 95%; -61.71 to -21.89
	Parameter Dispersion	Type: Standard Error of the mean; Value: 10.02
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	From day of first dose until 7 days after last dose
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo	Linagliptin
Arm/Group Description	Patients randomized to receive treatment with matching placebo	Patients randomized to receive treatment with Linagliptin 5 mg
All-Cause Mortality
	Placebo	Linagliptin
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Placebo	Linagliptin
	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/177 (2.26%)	18/523 (3.44%)
Cardiac disorders
Angina pectoris † 1	0/177 (0.00%)	1/523 (0.19%)
Atrial fibrillation † 1	0/177 (0.00%)	1/523 (0.19%)
Myocardial infarction † 1	0/177 (0.00%)	1/523 (0.19%)
Myocardial ischaemia † 1	0/177 (0.00%)	1/523 (0.19%)
Gastrointestinal disorders
Dyspepsia † 1	0/177 (0.00%)	1/523 (0.19%)
General disorders
Non-cardiac chest pain † 1	0/177 (0.00%)	1/523 (0.19%)
Infections and infestations
Blebitis † 1	0/177 (0.00%)	1/523 (0.19%)
Gastroenteritis † 1	0/177 (0.00%)	1/523 (0.19%)
Gastroenteritis viral † 1	0/177 (0.00%)	1/523 (0.19%)
Hepatitis viral † 1	1/177 (0.56%)	0/523 (0.00%)
Injury, poisoning and procedural complications
Avulsion fracture † 1	0/177 (0.00%)	1/523 (0.19%)
Snake bite † 1	0/177 (0.00%)	1/523 (0.19%)
Ulna fracture † 1	0/177 (0.00%)	1/523 (0.19%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion † 1	1/177 (0.56%)	1/523 (0.19%)
Nervous system disorders
Cerebral ischaemia † 1	1/177 (0.56%)	0/523 (0.00%)
Headache † 1	1/177 (0.56%)	0/523 (0.00%)
Renal and urinary disorders
Calculus ureteric † 1	0/177 (0.00%)	2/523 (0.38%)
Nephrolithiasis † 1	0/177 (0.00%)	2/523 (0.38%)
Renal mass † 1	0/177 (0.00%)	1/523 (0.19%)
Reproductive system and breast disorders
Rectocele † 1	1/177 (0.56%)	0/523 (0.00%)
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity † 1	0/177 (0.00%)	1/523 (0.19%)
Pulmonary embolism † 1	0/177 (0.00%)	1/523 (0.19%)
Vascular disorders
Hypertension † 1	0/177 (0.00%)	1/523 (0.19%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 12.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	Linagliptin
	Affected / at Risk (%)	Affected / at Risk (%)
Total	34/177 (19.21%)	54/523 (10.33%)
Infections and infestations
Nasopharyngitis † 1	9/177 (5.08%)	27/523 (5.16%)
Metabolism and nutrition disorders
Hyperglycaemia † 1	26/177 (14.69%)	27/523 (5.16%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 12.0

Limitations and Caveats

[Not Specified]

More Information

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
• EMail: clintriage.rdg@boehringer-ingelheim.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Del Prato S, Patel S, Crowe S, von Eynatten M. Efficacy and safety of linagliptin according to patient baseline characteristics: A pooled analysis of three phase 3 trials. Nutr Metab Cardiovasc Dis. 2016 Oct;26(10):886-92. doi: 10.1016/j.numecd.2016.06.015. Epub 2016 Jul 1.

• Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT00601250
• Other Study ID Numbers: 1218.17; 2007-002457-24 ( EudraCT Number: EudraCT )
• First Submitted: January 15, 2008
• First Posted: January 28, 2008
• Results First Submitted: May 13, 2011
• Results First Posted: June 7, 2011
• Last Update Posted: January 28, 2014