Efficacy and Safety Study of Linagliptin (5 mg Administered Orally Once Daily) Over 24 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite Metformin Therapy

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01215097
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 306
• Locations: 19
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 16.1
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

In this randomised, double-blind, parallel group trial, the safety and efficacy of 5 mg of Linagliptin administered orally once daily will be compared with a placebo after 24 weeks of treatment as add-on therapy to metformin in patients with type 2 diabetes and insufficient glycaemic control.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 306 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 Over 24 Weeks in T2D Patients With Insufficient Glycaemic Control Despite Metformin Therapy
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Linagliptin once a day	Drug: Linagliptin; once a day
Placebo Comparator: placebo once a day	Drug: placebo; once a day

Outcome Measures

Primary Outcome Measures

1. HbA1c Change From Baseline at Week 24 [Baseline and at week 24]

   Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

Secondary Outcome Measures

1. HbA1c Change From Baseline at Week 6 [Baseline and at week 6]

   Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

2. HbA1c Change From Baseline at Week 12 [Baseline and at week 12]

   Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

3. HbA1c Change From Baseline at Week 18 [Baseline and at week 18]

   Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

4. HbA1c Change From Baseline at Week 24(Chinese Only) [Baseline and at 24 weeks]

   Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.

5. FPG Change From Baseline at Week 24 [Baseline and at week 24]

   Means are treatment adjusted for baseline fasting plasma glucose (FPG) and previous anti-diabetic medication.

6. FPG Change From Baseline at Week 6 [Baseline and at week 6]

   Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.

7. FPG Change From Baseline at Week 12 [Baseline and at week 12]

   Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.

8. FPG Change From Baseline at Week 18 [Baseline and at week 18]

   Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.

9. Number of Patients With HbA1c < 7.0% [baseline and at week 24]

   Number of patients with HbA1c < 7.0% at week 24

10. Number of Patients With HbA1c < 7.0% at Week 24 With Baseline HbA1c >= 7.0%. [baseline and at week 24]

    Number of patients with HbA1c < 7.0% at week 24 with baseline HbA1c >= 7.0%.

11. Number of Patients With HbA1c < 6.5% [baseline and at week 24]

    Number of patients with HbA1c < 6.5% at week 24

12. Number of Patients With HbA1c < 6.5% at Week 24 With Baseline HbA1c >= 6.5%. [baseline and at week 24]

    Number of patients with HbA1c < 6.5% at week 24 with baseline HbA1c >= 6.5%.

13. Number With HbA1c at Least Lowering 0.5% [baseline and at week 24]

    Number with HbA1c at least 0.5% lowering from baseline at week 24

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Male and female patients with a diagnosis of type 2 diabetes mellitus and previously treated with metformin alone, or with metformin and not more than one other oral antidiabetic drug (antidiabetic therapy has to be unchanged for 6 weeks prior to informed consent and patients should receive standard diet and exercise counseling) A dose of >/=1500 mg/day metformin is required for inclusion into the trial. The dosage needs to be stable for at least 8 weeks before randomisation. Patients with a total daily dose of less than 1500 mg metformin will only be included; if the investigator has documented them to be on their maximum tolerated dose (also in this case the 8 week time interval will apply for a stable dose).

2. Diagnosis of type 2 diabetes prior to informed consent

3. Glycosylated haemoglobin A1 (HbA1c) at Visit 1a (Screening):

For patients undergoing wash out of previous medication: HbA1c =7.0 to =9.5% For patients not undergoing wash-out of previous medication: HbA1c =7.0 to =10.0%

1. Glycosylated haemoglobin A1 (HbA1c) =7.0 to =10.0% at Visit 2 (Start of Run-in)

2. Age = 18 and < 80 years at Visit 1a (Screening)

3. BMI (Body Mass Index) = 45 kg/m2 at Visit 1a (Screening)

4. Signed and dated written informed consent by date of Visit 1a in accordance with GCP and local legislation

Exclusion criteria:

1. Myocardial infarction, stroke or TIA within 6 months prior to informed consent

2. Impaired hepatic function, defined by serum levels of either Alanine transaminase,Aspartate transaminase, or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at Visit 1a

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

4. Known hypersensitivity or allergy to the investigational product or its excipients or metformin or placebo

5. Treatment with rosiglitazone or pioglitazone within 3 months prior to informed consent

6. Treatment with an injectable Glucagon-like peptide- 1 (GLP-1) analogue (e.g. exenatide) , Dipeptidyl-Peptidase 4 (DPP-IV) inhibitor within 3 months prior to informed consent

7. Treatment with insulin within 3 months prior to informed consent

8. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat, rimonabant) within 3 months prior to informed consent.

9. Alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or drug abuse

10. Participation in another trial with an investigational drug within 2 months prior to informed consent

11. Pre-menopausal women (last menstruation =1 year prior to informed consent) who:

• are nursing or pregnant,

• or are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include transdermal patch, intra-uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner. No exception will be made.

1. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.

2. Renal failure or renal impairment (serum creatinine =1.5 mg/dl as determined at Visit 1a)

3. Dehydration by clinical judgement of the investigator

4. Unstable or acute congestive heart failure

5. Acute or chronic metabolic acidosis (present in patient history)

6. Hereditary galactose intolerance

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1218.65.86007 Boehringer Ingelheim Investigational Site	Beijing		China
2	1218.65.86011 Boehringer Ingelheim Investigational Site	Chongqing		China
3	1218.65.86008 Boehringer Ingelheim Investigational Site	Dalian		China
4	1218.65.86010 Boehringer Ingelheim Investigational Site	Fuzhou		China
5	1218.65.86014 Boehringer Ingelheim Investigational Site	Hangzhou		China
6	1218.65.86005 Boehringer Ingelheim Investigational Site	Hefei		China
7	1218.65.86006 Boehringer Ingelheim Investigational Site	Hefei		China
8	1218.65.86012 Boehringer Ingelheim Investigational Site	Nanjing		China
9	1218.65.86001 Boehringer Ingelheim Investigational Site	Shanghai		China
10	1218.65.86002 Boehringer Ingelheim Investigational Site	Shanghai		China
11	1218.65.86003 Boehringer Ingelheim Investigational Site	Shanghai		China
12	1218.65.86004 Boehringer Ingelheim Investigational Site	Suzhou		China
13	1218.65.86015 Boehringer Ingelheim Investigational Site	Wenzhou		China
14	1218.65.86009 Boehringer Ingelheim Investigational Site	Wuhan		China
15	1218.65.86013 Boehringer Ingelheim Investigational Site	Yangzhou		China
16	1218.65.60002 Boehringer Ingelheim Investigational Site	Johor Bahru,		Malaysia
17	1218.65.60001 Boehringer Ingelheim Investigational Site	Kelantan		Malaysia
18	1218.65.63001 Boehringer Ingelheim Investigational Site	Marikina		Philippines
19	1218.65.63002 Boehringer Ingelheim Investigational Site	San Juan		Philippines

Sponsors and Collaborators

• Boehringer Ingelheim
• Eli Lilly and Company

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01215097
• Other Study ID Numbers: 1218.65
• First Posted: Oct 6, 2010
• Last Update Posted: Aug 25, 2016
• Last Verified: Jul 1, 2016

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

Study Results

Participant Flow

Recruitment Details	A total of 614 patients were screened in 19 centres in China, Malaysia,and Philippines.A total of 306 patients were randomised in a 1:2 ratio to receive either placebo (101 patients) or linagliptin 5 mg (205 patients) in addition to metformin.

Arm/Group Title	Placebo	Linagliptin 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Period Title: Overall Study
STARTED	100	205
COMPLETED	88	191
NOT COMPLETED	12	14

Baseline Characteristics

Arm/Group Title	Placebo	Linagliptin 5mg	Total
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral	Total of all reporting groups
Overall Participants	100	205	305
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.5 (8.7)	55.1 (10.7)	55.5 (10.1)
Sex: Female, Male (Count of Participants)
Female	50 50%	103 50.2%	153 50.2%
Male	50 50%	102 49.8%	152 49.8%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.8 (4.0)	25.5 (3.9)	25.6 (4.0)
Baseline HbA1c (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	8.00 (0.80)	7.99 (0.83)	7.99 (0.82)
Baseline fasting plasma glucose (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	157.7 (36.8)	160.5 (40.1)	159.6 (39.0)

Outcome Measures

1. Primary Outcome

Title	HbA1c Change From Baseline at Week 24
Description	Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time Frame	Baseline and at 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 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	97	203
Least Squares Mean (Standard Error) [Percent]	-0.14 (0.07)	-0.66 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.52
	Confidence Interval	() 95%; -0.70 to -0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

2. Secondary Outcome

Title	HbA1c Change From Baseline at Week 6
Description	Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time Frame	Baseline and at 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 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	97	203
Least Squares Mean (Standard Error) [Percent]	-0.02 (0.052)	-0.455 (0.037)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.433
	Confidence Interval	(2-Sided) 95%; -0.555 to -0.311
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.062
	Estimation Comments

3. Secondary Outcome

Title	HbA1c Change From Baseline at Week 12
Description	Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time Frame	Baseline and at 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 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	97	203
Least Squares Mean (Standard Error) [Percent]	-0.062 (0.068)	-0.653 (0.048)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.591
	Confidence Interval	() 95%; -0.752 to -0.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.082
	Estimation Comments

4. Secondary Outcome

Title	HbA1c Change From Baseline at Week 18
Description	Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time Frame	Baseline and at 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 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	97	203
Least Squares Mean (Standard Error) [Percent]	-0.119 (0.073)	-0.645 (0.052)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.53
	Confidence Interval	() 95%; -0.70 to -0.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

5. Secondary Outcome

Title	HbA1c Change From Baseline at Week 24(Chinese Only)
Description	Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication.
Time Frame	Baseline and at 24 weeks

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 (Chinese only). Last observation carried forward (LOCF) was used as the imputation rule.

Arm/Group Title	Placebo	Linagliptin 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	77	182
Least Squares Mean (Standard Error) [Percent]	-0.16 (0.08)	-0.68 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.52
	Confidence Interval	() 95%; -0.71 to -0.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments

6. Secondary Outcome

Title	FPG Change From Baseline at Week 24
Description	Means are treatment adjusted for baseline fasting plasma glucose (FPG) and previous anti-diabetic medication.
Time Frame	Baseline and at 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 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	97	203
Least Squares Mean (Standard Error) [mg/dL]	-1.1 (3.5)	-10.7 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0233
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-9.6
	Confidence Interval	() 95%; -17.8 to -1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.2
	Estimation Comments

7. Secondary Outcome

Title	FPG Change From Baseline at Week 6
Description	Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.
Time Frame	Baseline and at 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 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	97	203
Least Squares Mean (Standard Error) [mg/dL]	5.3 (2.8)	-16.8 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-22.1
	Confidence Interval	() 95%; -28.7 to -15.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.3
	Estimation Comments

8. Secondary Outcome

Title	FPG Change From Baseline at Week 12
Description	Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.
Time Frame	Baseline and at 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 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	97	203
Least Squares Mean (Standard Error) [mg/dL]	-4.5 (3.0)	-14.7 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0050
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-10.2
	Confidence Interval	() 95%; -17.3 to -3.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.6
	Estimation Comments

9. Secondary Outcome

Title	FPG Change From Baseline at Week 18
Description	Means are treatment adjusted for baseline FPG and previous anti-diabetic medication.
Time Frame	Baseline and at 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 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	97	203
Least Squares Mean (Standard Error) [mg/dL]	-1.9 (3.4)	-13.4 (2.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0044
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-11.5
	Confidence Interval	() 95%; -19.5 to -3.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.0
	Estimation Comments

10. Secondary Outcome

Title	Number of Patients With HbA1c < 7.0%
Description	Number of patients with HbA1c < 7.0% at week 24
Time Frame	baseline and at 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. Non-completers were considered as failure imputation (NCF).

Arm/Group Title	Placebo	Linagliptin 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	97	203
Number [Participants]	14 14%	82 40%

11. Secondary Outcome

Title	Number of Patients With HbA1c < 7.0% at Week 24 With Baseline HbA1c >= 7.0%.
Description	Number of patients with HbA1c < 7.0% at week 24 with baseline HbA1c >= 7.0%.
Time Frame	baseline and at 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 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	89	185
Number [Participants]	9 9%	69 33.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments	Comparison by odds ratio for the patients with a baseline HbA1c >=7.0%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments	The odds-ratio is based on a logistic regression model including baseline HbA1c and previous antidiabetic medication
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	6.243
	Confidence Interval	() 95%; 2.831 to 13.769
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Number of Patients With HbA1c < 6.5%
Description	Number of patients with HbA1c < 6.5% at week 24
Time Frame	baseline and at 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. Non-completers were considered as failure imputation (NCF).

Arm/Group Title	Placebo	Linagliptin 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	97	203
Number [Participants]	4 4%	26 12.7%

13. Secondary Outcome

Title	Number of Patients With HbA1c < 6.5% at Week 24 With Baseline HbA1c >= 6.5%.
Description	Number of patients with HbA1c < 6.5% at week 24 with baseline HbA1c >= 6.5%.
Time Frame	baseline and at 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 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	96	202
Number [Participants]	3 3%	26 12.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments	Comparison by odds ratio for the patients with a baseline HbA1c >= 6.5%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0129
	Comments
	Method	Regression, Logistic
	Comments	The odds-ratio is based on a logistic regression model including baseline HbA1c and previous antidiabetic medication
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.97
	Confidence Interval	() 95%; 1.404 to 17.592
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Number With HbA1c at Least Lowering 0.5%
Description	Number with HbA1c at least 0.5% lowering from baseline at week 24
Time Frame	baseline and at 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. Non-completers were considered as failure imputation (NCF).

Arm/Group Title	Placebo	Linagliptin 5mg
Arm/Group Description	Placebo	Linagliptin 5mg, once daily tablets, oral
Measure Participants	97	203
Number [Participants]	33 33%	120 58.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Linagliptin 5mg
	Comments	Comparison by odds ratio for the patients with HbA1c at least lowering 0.5% from baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments	The odds-ratio is based on a logistic regression model including baseline HbA1c and previous antidiabetic medication
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.054
	Confidence Interval	() 95%; 1.799 to 5.185
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	24 weeks
Arm/Group Title	Placebo		Linagliptin 5mg
Arm/Group Description	Placebo		Linagliptin 5mg, once daily tablets, oral
All Cause Mortality
	Placebo		Linagliptin 5mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Linagliptin 5mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/100 (2%)		4/205 (2%)
Hepatobiliary disorders
Cholecystitis	1/100 (1%)		0/205 (0%)
Injury, poisoning and procedural complications
Comminuted fracture	0/100 (0%)		1/205 (0.5%)
Investigations
Alanine aminotransferase increased	0/100 (0%)		1/205 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	0/100 (0%)		1/205 (0.5%)
Nervous system disorders
Lacunar infarction	1/100 (1%)		0/205 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/100 (0%)		1/205 (0.5%)
Other (Not Including Serious) Adverse Events
	Placebo		Linagliptin 5mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/100 (13%)		29/205 (14.1%)
Gastrointestinal disorders
Diarrhoea	1/100 (1%)		5/205 (2.4%)
Infections and infestations
Upper respiratory tract infection	3/100 (3%)		3/205 (1.5%)
Nasopharyngitis	1/100 (1%)		5/205 (2.4%)
Metabolism and nutrition disorders
Hyperlipidaemia	4/100 (4%)		9/205 (4.4%)
Hyperglycaemia	5/100 (5%)		10/205 (4.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.