Effect of Linagliptin on Insulin Sensitivity and Pancreatic Beta Cell Function in Patients With Type 2 Diabetes Mellitus

April 6, 2014 updated by: Anil Bhansali, Postgraduate Institute of Medical Education and Research

A Randomized Double-blind Study to Evaluate the Effect of Linagliptin on Pancreatic Beta Cell Function and Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus on Metformin Monotherapy

This study is planned to evaluate if linagliptin can improve insulin sensitivity in patients with type 2 diabetes mellitus. In addition, the effect of linagliptin on pancreatic function will be studied.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

This is a prospective study of 30 patients with type 2 diabetes mellitus (T2DM) . Patients with T2DM in the age group 30-65 years and duration of diabetes less than five years will be screened. After exclusion, those who meet the inclusion criteria will be included in the study.

Once eligibility criteria are confirmed, patients will be educated about their disease and will be advised weight maintenance diabetic diet and exercise throughout the study period. Patients will be randomized to three groups - linagliptin (5mg OD) or voglibose (0.2mg TDS) or placebo OD. Metformin will be continued in all patients. To evaluate the effect of linagliptin on insulin sensitivity and beta cell function, independent of changes in HbA1c, the voglibose group is included. Each group will have 10 patients and will be followed up for 6 months. Both patients and physicians will be blinded to the treatment.

After having written informed consent, a detailed history and a thorough clinical examination will be done in all subjects including measurement of height, weight, body mass index and waist circumference. Hemoglobin, liver function tests, renal function tests, lipid profile, HbA1c, fasting plasma insulin , C-peptide, homeostasis model assessment-insulin resistance index(HOMA-1R) and homeostasis model assessment-beta cell function index (HOMA-β) will be done at baseline. A euglycemic hyperinsulinemic clamp study and a mixed meal test will be performed in all patients (on different days) at baseline and after 6 months of follow up. Biochemical parameters will be measured again 6 months after therapy. Fasting and post-prandial blood glucose will be done monthly for 6 months.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with type 2 diabetes mellitus (according to ADA guidelines)
  • Age between 30-65 years
  • Duration of diabetes less than five years
  • BMI of between 20 and 40 kg/m2
  • HbA1c level of < 7.5%
  • On metformin monotherapy for at least 6 weeks

Exclusion Criteria:

  • History of ketoacidosis
  • Hepatic impairment (defined as plasma aminotransferase elevations of more than 3 times upper limit of normal)
  • Renal failure (defined as Serum Creatinine more than 1.5 mg/dl)
  • Coronary artery disease or heart failure
  • Cerebrovascular disease or stroke
  • Anemia (Hb< 10 g/dl)
  • Those who requires insulin therapy HbA1c >7.5%
  • Presence of macular edema
  • Pregnant or lactating women
  • Patients who have received dipeptidyl peptidase 4 (DPP-4) inhibitor therapy within last 3 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Linagliptin
Tablet Linagliptin (5mg) per oral, once daily will be given to 10 patients for 6 months
Drug: Linagliptin
Tablet Linagliptin (5mg) per oral, once daily will be given to 10 patients for 6 months
Other Names:
  • Trajenta 5mg
Placebo Comparator: Placebo
Tablet Placebo per oral, once daily will be given to 10 patients for 6 months
Drug: Placebo
Tablet placebo per oral, once daily will be given to 10 patients for 6 months
Active Comparator: Voglibose
Tablet Voglibose (0.2mg) per oral, thrice daily (with meals) will be given to 10 patients for 6 months
Drug: Voglibose
Tablet Voglibose (0.2mg) per oral thrice daily(with meals) to 10 patients for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To study the effect of Linagliptin on insulin sensitivity by performing euglycemic hyperinsulinemic clamp in patients with type 2 diabetes mellitus.
Time Frame: 6 months

Hyperinsulinemic euglycemic clamp of 2 hours duration will be done at baseline and after 6 months of treatment in all patients. Medications taken by the patient will be omitted on the day of test.After an overnight fast of 10 hours, intravenous catheter will be inserted, under sterile precautions, into the antecubital vein for infusion of insulin and dextrose solutions, while another catheter will be inserted in an anti-flow direction into the dorsal vein of the contralateral hand for arterialized blood sampling.

An insulin infusate of 300 mU/ml will be administered at a constant rate, after an initial priming dose, while a 25 percent dextrose solution is administered at varying rates to maintain blood glucose at 90 mg/dl. Blood glucose will be analyzed by a bedside glucose analyzer every 5 minutes. M value, a measure of glucose utilisation will be calculated during the steady state (last 30 minutes of the test)
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To study the effects of Linagliptin on glycemic control and beta cell function in patients with type 2 diabetes mellitus 6 months
Time Frame: 6 months

Fasting and 2 hour postprandial blood glucose will be at baseline and after 6 months of treatment. HbA1C will be done at baseline and after 3 and 6 months.

HOMA-IR and HOMA-β will be done at baseline and after 6 months. Patients will also be subjected to a mixed meal test at baseline and at 6 months. Mixed meal test will be done 3-7 days after clamp study. After an overnight fast of 10 hours, patients will be given standardized mixed meal, 2.5 g/ kg. (Ensure, Abbott Nutrition, Abbott Laboratories) Medications normally taken by the subject in the morning will be administered 20 min prior to the start of the test meal. Samples for glucose, insulin, C-peptide and glucagon-like peptide-1 (GLP-1) will be taken at 0,30,60,90,120,150 and 180 minutes following the ingestion of meal. Total area under curves for glucose, insulin, C-peptide and GLP-1 from pre meal to 180 min will be calculated using the trapezoidal rule.
6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
To study the effect of voglibose on glucagon like peptide1 (GLP1) secretion and insulin resistance in patients with type 2 diabetes mellitus 6 months
Time Frame: 6 months
Patients will be subjected to mixed meal test and a hyperinsulinemic euglycemic clamp study at baseline and after 6 months of treatment.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Postgraduate Institute of Medical Education and Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2013

Primary Completion (Anticipated)

November 1, 2014

Study Completion (Anticipated)

January 1, 2015

Study Registration Dates

First Submitted

March 24, 2014

First Submitted That Met QC Criteria

March 24, 2014

First Posted (Estimate)

March 27, 2014

Study Record Updates

Last Update Posted (Estimate)

April 8, 2014

Last Update Submitted That Met QC Criteria

April 6, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Linagliptin

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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