Study to Compare the Efficacy and Safety of Administration of the Fix Dose Combination of Linagliptin Plus Metformin in Drug naïve Type 2 Patients

This study has been completed.
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim Identifier:
First received: October 16, 2012
Last updated: May 13, 2014
Last verified: May 2014

Reduced factorial design study with 24 week randomized treatment of initial combination therapy with linagliptin and metformin in T2DM patients

Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: linagliptin2.5mg/metformin1000mg
Drug: linagliptin 5mg
Drug: Metformin 500mg
Drug: linagliptin2.5mg/metformin500mg
Drug: Metformin 1000mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase III Randomised, Double-blind, Double-dummy, Parallel Group Study to Compare the Efficacy and Safety of Twice Daily Administration of the Fix Dose Combination of Linagliptin 2.5 mg + Metformin 500 mg, or of Linagliptin 2.5 mg + Metformin 1000 mg, With the Individual Components of Metformin (500 mg or 1000 mg, Twice Daily), and Linagliptin (5.0 mg, Once Daily) Over 24 Weeks in Treatment naïve Type 2 Diabetic Patients With Insufficient Glycaemic Control

Resource links provided by NLM:

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • The change from baseline in HbA1c after 24 weeks of treatment (for both in main group and additional parallel group). [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The occurrence of treat to target efficacy response in terms of HbA1c < 7.0 % and < 6.5% after 24 weeks of treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • The occurrence of relative efficacy response (HbA1c lowering by at least 0.5% after 24 weeks of treatment) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • The change in fasting plasma glucose (FPG) from baseline after 24 weeks of treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • The frequency of patients with use of rescue therapy during 24 week treatment period. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 876
Study Start Date: October 2012
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: linagliptin2.5mg / metformin500mg BID
patient to receive a tablet containing linagliptin 2.5mg and metformin 500mg BID
Drug: linagliptin 5mg
linagliptin 5mg once daily
Drug: Metformin 500mg
Metformin 500mg BID
Experimental: linagliptin2.5mg / metformin1000mg BID
patient to receive a tablet containing linagliptin 2.5mg and metformin 1000mg BID
Drug: linagliptin 5mg
linagliptin 5mg once daily
Drug: Metformin 1000mg
Metformin 1000mg BID
Active Comparator: metformin 500mg BID
patient to receive a tablet containing metformin 500mg BID
Drug: linagliptin2.5mg/metformin500mg
linagliptin2.5mg/metformin500mg BID
Active Comparator: metformin 1000mg BID
patient to receive a tablet containing metformin 1000mg BID
Drug: linagliptin2.5mg/metformin1000mg
linagliptin2.5mg/metformin1000mg BID
Active Comparator: linagliptin 5 mg QD
patient to receive a tablet containing linagliptin 5mg once daily
Drug: linagliptin2.5mg/metformin1000mg
linagliptin2.5mg/metformin1000mg BID
Drug: linagliptin2.5mg/metformin500mg
linagliptin2.5mg/metformin500mg BID


Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Diagnosis of Type 2 diabetes mellitus(T2DM) prior to informed consent
  2. Male and female patients on diet and exercise regimen who are drug-naïve
  3. Glycosylated haemoglobin A1c (HbA1c) at V1a >/=7.5 %<11% for main group and HbA1c >/= 11.0 % for the additional parallel group
  4. Age >/= 18 and </= 80 years at Visit 1a (Screening)
  5. Body Mass Index(BMI)</ = 40 kg/m2 at Visit 1a (Screening)
  6. Signed and dated written informed consent by date of Visit 1a in accordance with good clinical practice(GCP) and local legislation

Exclusion criteria:

  1. Uncontrolled hyperglycaemia required for rescue medication during placebo run-in phase
  2. In main group, the patients with investigational medicinal product(IMP) compliance < 80 % or >120 % during 2 weeks placebo run in period
  3. Acute coronary syndrome stroke or Transient ischaemic attack (TIA) within 3 months prior to randomisation
  4. Impaired hepatic function, defined by serum levels of either Alanine aminotransferase(ALT) ,Aspartate aminotransferase(AST), or alkaline phosphatase (AP) above 3 x upper limit of normal (ULN) ,or total bilirubin above 1.5 x ULN as determined at Visit 1a
  5. Known hypersensitivity or allergy to linagliptin or its excipients or metformin or placebo
  6. Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at the time of screening
  7. 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.
  8. Concurrent participation in another clinical trial or any investigational therapy within thirty days prior to signing the consent form or during the trial.
  9. 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
  10. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.
  11. Renal failure or renal impairment at Visit 1a (screening) with an Estimated Glomerular Filtration Rate(eGFR) < 60 ml/min
  12. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
  13. Dehydration by clinical judgement of the investigator
  14. Clinical detected unstable or acute congestive heart failure
  15. Acute or chronic metabolic acidosis (present in patient history)
  16. Hereditary galactose intolerance
  17. Known history of pancreatitis and chronic pancreatitis
  18. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within last 5 years.
  19. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial at the discretion of investigator
  Contacts and Locations
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Please refer to this study by its identifier: NCT01708902

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Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim Identifier: NCT01708902     History of Changes
Other Study ID Numbers: 1288.18
Study First Received: October 16, 2012
Last Updated: May 13, 2014
Health Authority: China: Food and Drug Administration
Malaysia: Ministry of Health
Philippines: Bureau of Food and Drugs
Vietnam: Ministry of Health

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors processed this record on March 26, 2015