Linagliptin Add-on to Insulin Background Therapy

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02897349
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 206
• Locations: 25
• Arms: 2
• Actual Duration (Months): 27.6
• Patients Per Site: 8.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of linagliptin compared to placebo when added on to insulin therapy alone or in combination with metformin in Chinese patients with type 2 diabetes mellitus with insufficient glycaemic control

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: placebo; Drug: linagliptin; Drug: background therapy	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 206 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomised, Double-blind, Placebo-controlled, Parallel Group, Efficacy and Safety Study of Linagliptin, Administered Orally Once Daily, in Combination With Insulin Therapy for 24 Weeks in Chinese Type 2 Diabetes Mellitus Patients With Insufficient Glycaemic Control
• Actual Study Start Date: Sep 30, 2016
• Actual Primary Completion Date: Jan 11, 2019
• Actual Study Completion Date: Jan 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: linagliptin	Drug: linagliptin; Drug: background therapy; insulin with or without metformin
Placebo Comparator: Placebo	Drug: placebo; Drug: background therapy; insulin with or without metformin

Outcome Measures

Primary Outcome Measures

1. Percentage Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment [Baseline and week 24]

   Percentage change from baseline, that is, [[(HbA1c after 24 weeks of treatment) - (HbA1c at baseline)] / (HbA1c at baseline)] *100%, where baseline refers to the last observation prior to the start of randomised study drug, including the observation prior to the placebo run-in.

Secondary Outcome Measures

1. Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment [Baseline and week 24]

   Change from baseline in Fasting plasma glucose (FPG) after 24 weeks of treatment.

2. Change From Baseline in 2-hour (2-h) Postprandial Plasma Glucose (PPG) After 24 Weeks of Treatment [Baseline and week 24]

   Change from baseline in 2-hour (2-h) postprandial plasma glucose (PPG) after 24 weeks of treatment.

3. Percentage of Participants With HbA1c on Treatment <7.0 Percentage (%) After 24 Weeks of Treatment [24 weeks]

   Percentage of participants with HbA1c on treatment <7.0 percentage (%) after 24 weeks of treatment. Participants with baseline HbA1c <7.0% were excluded from the analysis.

4. Percentage of Participants With HbA1c on Treatment < 6.5% After 24 Weeks of Treatment [24 weeks]

   Percentage of participants with HbA1c on treatment < 6.5% after 24 weeks of treatment. Participants with baseline HbA1c <6.5% were excluded from the analysis.

5. Percentage of Participants With HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment [24 weeks]

   Percentage of participants with HbA1c lowering by at least 0.5% after 24 weeks of treatment.

6. Percentage of Participants With Any Investigator-defined Hypoglycaemic Adverse Event (AE) With Plasma Glucose (PG) ≤70 mg/dL [24 weeks]

   Incidence of investigator-reported hypoglycaemic events confirmed by a measured blood glucose ≤70 mg/dL (≤3.9 Millimoles Per Litre (mmol/L)). Severe hypoglycaemic AE = hypoglycaemic event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions.

7. Percentage of Participants With Any Severe Hypoglycaemic AE [24 weeks]

   Incidence of severe hypoglycaemic events (requiring active assistance by another person, or fatal). Severe hypoglycaemic AE = hypoglycaemic event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions.

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Diagnosis of type 2 diabetes mellitus prior to informed consent.

• Chinese male or female patients who are pre-treated with insulin alone or in combination with metformin:

• With maximum insulin dose of <= 1 unit/kg/day. Acceptable basal insulins could be insulin glargin, insulin detemir or NPH (neutral protamin hagedorn) insulin with duration of action up to 24 h; acceptable pre-mixed insulins could be preparations with 25/75 or 30/70 ratio, with once or twice daily posology only. The total insulin dose should not be changed by more than 10% of the baseline value within the 12 weeks prior to randomisation (Visit 3). Both human insulin & insulin analogue are accepted.

• If the patient is taking metformin, stable dose (at least 1500 mg daily) must be maintained for at least 12 weeks without dose adjustments prior to randomisation (Visit 3).

• HbA1c fulfills the following criteria: >= 7.5 % to <= 10.0 % at Visit 1.

• Age >= 18 years at Visit 1.

• BMI <= 45 kg/m2 (Body Mass Index) at Visit 1.

• Women of childbearing potential must be ready and able to use highly effective methods of birth control per ICH (International Conference on Harmonisation) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.

• A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile.

• Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

• Signed and dated written informed consent by date of Visit 1 in accordance with ICH-GCP (Good Clinical Practice) and local legislation

Exclusion criteria:

• Uncontrolled hyperglycaemic with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day).

• Any other antidiabetic drug within 3 months prior to informed consent except those defined as background treatment via inclusion criterion 2.

• Acute coronary syndrome (non-STEMI (ST Segment Elevation Myocardial Infarction), STEMI and unstable angina pectoris), stroke or TIA (Transient ischemic attack) within 3 months prior to informed consent.

• Indication of liver disease, defined by serum levels of either ALT (Alanine aminotransferase) (SGPT (serum glutamic pyruvate transaminase )), AST (Aspartate aminotransferase) (SGOT (serum glutamic-oxaloacetic transaminase)), or alkaline phosphatase above 3 × upper limit of normal (ULN (upper limit of normal)) as determined during screening and/or run-in phase.

• Any contraindications to metformin according to the local label for those patients that enter the study with metformin therapy as provided in ISF (Investigator Site File).

• Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.

• Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years.

• Blood dyscrasias or any disorders causing hemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia).

• Known hypersensitivity or allergy to the investigational product or its recipients.

• Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight.

• Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM (Type 2 diabetes mellitus).

• Women who are pregnant, nursing, or who plan to become pregnant while in the trial.

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

• Participation in another trial with an investigational drug within 2 months prior to informed consent or previous enrolment in this trial.

• Any other clinical condition that would jeopardize patient's safety while participating in this clinical trial in the opinion of the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	China-Japan Friendship Hospital	Beijing		China	100029
2	Beijing Tongren Hospital	Beijing		China	100730
3	The General Hospital of Chinese People's Armed Police Forces	Beijing		China	100854
4	First Hospital of Jilin University	Changchun		China	130021
5	No.900 Hospital of PLA Joint Logistics Support Force	Fuzhou		China	350025
6	Third Affiliated Hospital of Guangzhou Medical University	Guangzhou		China	510150
7	The Affiliated Hospital of Guizhou Medical University	Guiyang		China	550004
8	The Affiliated Hospital of Hangzhou Normal University	Hangzhou		China	310015
9	General Hospital of Jinan Military Area	Jinan		China	250000
10	Nanjing First Hospital	Nanjing		China	210006
11	The affiliated hospital of medicalcollege qingdao university	Qingdao		China	266005
12	Centre Hospital of Putuo District, Shanghai	Shanghai		China	200062
13	Shanghai Tenth People's Hospital	Shanghai		China	200072
14	Yangpu Hospital, Tongji University	Shanghai		China	200090
15	Second Hospital Affiliated to Shantou Medical University	Shantou		China	515041
16	Shengjing Hospital of China Medical University	Shengyang		China	110072
17	Siping Central People's Hospital	Siping		China	136000
18	The First Affiliated Hospital of Soochow University	Suzhou		China	215006
19	Nankai University Affiliated Hospital	Tianjin		China	300000
20	The 2nd Hospital of Tianjin Medical University	Tianjin		China	300000
21	Tianjin Medical University General Hospital	Tianjin		China	30052
22	Renmin Hospital of Wuhan University	Wuhan		China	430060
23	First Affiliated Hospital of Xiamen University	Xiamen		China	361003
24	the first people hospital of Yue Yang	Yueyang		China	414000
25	Affiliated Hospital of Jiangsu University	Zhenjiang		China	212013

Sponsors and Collaborators

• Boehringer Ingelheim
• Eli Lilly and Company

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Statistical Analysis Plan - Feb 14, 2019
• Study Protocol - Nov 28, 2017

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02897349
• Other Study ID Numbers: 1218.102
• First Posted: Sep 13, 2016
• Last Update Posted: Mar 25, 2020
• Last Verified: Mar 1, 2020

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Linagliptin

Study Results

Participant Flow

Recruitment Details	This was a randomised, double-blind, multi-centre, and placebo-controlled, parallel group study to compare linagliptin with placebo as add-on therapy to stable insulin alone (basal insulin, premixed insulin) or in combination with metformin in Chinese type 2 diabetes mellitus (T2DM) participants with insufficient glycaemic control.
Pre-assignment Detail	All participants were screened for eligibility to participate in the trial. Participants attended specialist sites which would then ensure that all participants met all inclusion/exclusion criteria. Participants were not to be randomized to trial treatment if any one of the specific entry criteria were not met.

Arm/Group Title	Placebo Matching Linagliptin	Linagliptin
Arm/Group Description	Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Period Title: Overall Study
STARTED	102	104
COMPLETED	97	98
NOT COMPLETED	5	6

Baseline Characteristics

Arm/Group Title	Placebo Matching Linagliptin	Linagliptin	Total
Arm/Group Description	Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Total of all reporting groups
Overall Participants	102	104	206
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	57.1 (10.6)	60.1 (9.5)	58.7 (10.2)
Sex: Female, Male (Count of Participants)
Female	48 47.1%	52 50%	100 48.5%
Male	54 52.9%	52 50%	106 51.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	102 100%	104 100%	206 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	102 100%	104 100%	206 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment
Description	Percentage change from baseline, that is, [[(HbA1c after 24 weeks of treatment) - (HbA1c at baseline)] / (HbA1c at baseline)] *100%, where baseline refers to the last observation prior to the start of randomised study drug, including the observation prior to the placebo run-in.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) observed cases (OC): The FAS consisted of all patients randomised in the TS who had a baseline HbA1c value and at least one on-treatment HbA1c value. The FAS was the basis for the intention-to-treat (ITT) analysis.

Arm/Group Title	Placebo Matching Linagliptin	Linagliptin
Arm/Group Description	Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Measure Participants	99	100
Least Squares Mean (Standard Error) [Percentage change]	-0.20 (0.09)	-0.61 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Matching Linagliptin, Linagliptin
	Comments	Based on Mixed-effect Model Repeated Measures (MMRM) including fixed effects treatment, week, type of insulin, and treatment by week interaction, linear covariates baseline HbA1c, baseline HbA1c by week interaction and random effect for patient. Within-patient errors are modelled by unstructured covariance matrix. Adjusted mean is based on all patients in the model (not only patients with a baseline and week 24 measurement).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	Mixed model repeated measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference (%)
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.65 to -0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks of Treatment
Description	Change from baseline in Fasting plasma glucose (FPG) after 24 weeks of treatment.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

FAS (OC)

Arm/Group Title	Placebo Matching Linagliptin	Linagliptin
Arm/Group Description	Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Measure Participants	99	99
Least Squares Mean (Standard Error) [Milligram/Decilitre (mg/dL)]	0.7 (3.6)	-5.5 (3.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Matching Linagliptin, Linagliptin
	Comments	Based on MMRM including fixed effects treatment, week, type of insulin, and treatment by week interaction, linear covariates baseline HbA1c, baseline FPG baseline FPG by week interaction and random effect for patient. Within-patient errors are modelled by unstructured covariance matrix. Adjusted mean is based on all patients in the model (not only patients with a baseline and week 24 measurement).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2241
	Comments
	Method	Mixed model repeated measures
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference (mg/dL)
	Estimated Value	-6.2
	Confidence Interval	(2-Sided) 95%; -16.2 to 3.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.1
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in 2-hour (2-h) Postprandial Plasma Glucose (PPG) After 24 Weeks of Treatment
Description	Change from baseline in 2-hour (2-h) postprandial plasma glucose (PPG) after 24 weeks of treatment.
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

Meal tolerance test (MTT) (OC) set: MTT-set consisted all patients of the FAS with a valid MTT at baseline and at the end of the study. An MTT was considered valid if it had a valid FPG and a valid 2-h PPG value.

Arm/Group Title	Placebo Matching Linagliptin	Linagliptin
Arm/Group Description	Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Measure Participants	78	88
Least Squares Mean (Standard Error) [mg/dL]	-0.06 (5.98)	-32.01 (5.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Matching Linagliptin, Linagliptin
	Comments	Based on analysis of covariance (ANCOVA) model including fixed effect treatment and type of insulin, and linear covariates baseline HbA1c and baseline 2-h PPG.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference (mg/dL)
	Estimated Value	-31.95
	Confidence Interval	(2-Sided) 95%; -48.15 to -15.75
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.20
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With HbA1c on Treatment <7.0 Percentage (%) After 24 Weeks of Treatment
Description	Percentage of participants with HbA1c on treatment <7.0 percentage (%) after 24 weeks of treatment. Participants with baseline HbA1c <7.0% were excluded from the analysis.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) Non-completers considered as failure (NCF)

Arm/Group Title	Placebo Matching Linagliptin	Linagliptin
Arm/Group Description	Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Measure Participants	97	101
Number [Percentage of participants]	8.2 8%	13.9 13.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Matching Linagliptin, Linagliptin
	Comments	Logistic regression model with terms for treatment and type of insulin as fixed effect and continuous linear covariates baseline HbA1c
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2431
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.793
	Confidence Interval	(2-Sided) 95%; 0.673 to 4.780
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With HbA1c on Treatment < 6.5% After 24 Weeks of Treatment
Description	Percentage of participants with HbA1c on treatment < 6.5% after 24 weeks of treatment. Participants with baseline HbA1c <6.5% were excluded from the analysis.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

FAS (NCF)

Arm/Group Title	Placebo Matching Linagliptin	Linagliptin
Arm/Group Description	Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Measure Participants	100	101
Number [Percentage of participants]	3.0 2.9%	4.0 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Matching Linagliptin, Linagliptin
	Comments	Logistic regression model with terms for treatment and type of insulin as fixed effect and continuous linear covariates baseline HbA1c
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6235
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.481
	Confidence Interval	(2-Sided) 95%; 0.309 to 7.105
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With HbA1c Lowering by at Least 0.5% After 24 Weeks of Treatment
Description	Percentage of participants with HbA1c lowering by at least 0.5% after 24 weeks of treatment.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

FAS (NCF)

Arm/Group Title	Placebo Matching Linagliptin	Linagliptin
Arm/Group Description	Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Measure Participants	100	101
Number [Percentage of participants]	36.0 35.3%	55.4 53.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Matching Linagliptin, Linagliptin
	Comments	Logistic regression model with terms for treatment and type of insulin as fixed effect and continuous linear covariates baseline HbA1c
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0049
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.293
	Confidence Interval	(2-Sided) 95%; 1.286 to 4.091
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With Any Investigator-defined Hypoglycaemic Adverse Event (AE) With Plasma Glucose (PG) ≤70 mg/dL
Description	Incidence of investigator-reported hypoglycaemic events confirmed by a measured blood glucose ≤70 mg/dL (≤3.9 Millimoles Per Litre (mmol/L)). Severe hypoglycaemic AE = hypoglycaemic event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Treated set (TS) : The TS consisted of all patients treated with at least one dose of study drug.

Arm/Group Title	Placebo Matching Linagliptin	Linagliptin
Arm/Group Description	Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Measure Participants	102	104
Number [Percentage of Participants]	7.8 7.6%	10.6 10.2%

8. Secondary Outcome

Title	Percentage of Participants With Any Severe Hypoglycaemic AE
Description	Incidence of severe hypoglycaemic events (requiring active assistance by another person, or fatal). Severe hypoglycaemic AE = hypoglycaemic event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

TS

Arm/Group Title	Placebo Matching Linagliptin	Linagliptin
Arm/Group Description	Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.	Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
Measure Participants	102	104
Number [Percentage of Participants]	0.0 0%	0.0 0%

Adverse Events

Time Frame	From first drug administration until 7 days after the last drug administration, up to 176 days.
Arm/Group Title	Placebo Matching Linagliptin		Linagliptin
Arm/Group Description	Participants were administered placebo matching 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.		Participants were administered 5 milligram (mg) linagliptin tablet once daily per os (p.o.) for 24 weeks.
All Cause Mortality
	Placebo Matching Linagliptin		Linagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/102 (1%)		0/104 (0%)
Serious Adverse Events
	Placebo Matching Linagliptin		Linagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/102 (16.7%)		10/104 (9.6%)
Cardiac disorders
Angina pectoris	1/102 (1%)		0/104 (0%)
Angina unstable	0/102 (0%)		1/104 (1%)
Bundle branch block left	0/102 (0%)		1/104 (1%)
Coronary artery disease	1/102 (1%)		0/104 (0%)
Ear and labyrinth disorders
Conductive deafness	1/102 (1%)		0/104 (0%)
Deafness neurosensory	1/102 (1%)		0/104 (0%)
Eye disorders
Cataract	2/102 (2%)		1/104 (1%)
Ophthalmoplegia	1/102 (1%)		0/104 (0%)
Pterygium	1/102 (1%)		0/104 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/102 (1%)		0/104 (0%)
Large intestine polyp	0/102 (0%)		1/104 (1%)
Obstructive pancreatitis	0/102 (0%)		1/104 (1%)
Hepatobiliary disorders
Cholecystitis acute	0/102 (0%)		1/104 (1%)
Cholelithiasis	0/102 (0%)		1/104 (1%)
Drug-induced liver injury	1/102 (1%)		0/104 (0%)
Liver injury	1/102 (1%)		0/104 (0%)
Injury, poisoning and procedural complications
Fall	0/102 (0%)		1/104 (1%)
Humerus fracture	0/102 (0%)		1/104 (1%)
Patella fracture	1/102 (1%)		0/104 (0%)
Road traffic accident	1/102 (1%)		0/104 (0%)
Subcutaneous haematoma	1/102 (1%)		0/104 (0%)
Subdural haematoma	1/102 (1%)		0/104 (0%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/102 (1%)		0/104 (0%)
Diabetic ketoacidosis	0/102 (0%)		1/104 (1%)
Nervous system disorders
Cerebral infarction	1/102 (1%)		0/104 (0%)
Cerebral ischaemia	1/102 (1%)		0/104 (0%)
Diabetic neuropathy	0/102 (0%)		2/104 (1.9%)
Facial paralysis	1/102 (1%)		0/104 (0%)
Renal and urinary disorders
Acute kidney injury	0/102 (0%)		1/104 (1%)
Diabetic nephropathy	0/102 (0%)		1/104 (1%)
Glomerulonephritis chronic	0/102 (0%)		1/104 (1%)
Nephrolithiasis	1/102 (1%)		0/104 (0%)
Vascular disorders
Hypertension	1/102 (1%)		0/104 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Matching Linagliptin		Linagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/102 (25.5%)		33/104 (31.7%)
Infections and infestations
Upper respiratory tract infection	13/102 (12.7%)		14/104 (13.5%)
Metabolism and nutrition disorders
Hyperuricaemia	1/102 (1%)		6/104 (5.8%)
Hypoglycaemia	13/102 (12.7%)		18/104 (17.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.