Adjunctive Therapy of Exenatide or Sitagliptin to Insulin Glargine in Type 2 Diabetes

September 3, 2009 updated by: Profil Institut für Stoffwechselforschung GmbH

Acute Effect of a GLP-1-Analogue (Exenatide) and of a DPP-4-Inhibitor (Sitagliptin) in Subjects With Type 2 Diabetes Treated With Insulin Glargine Once Daily

This study investigated a 4-week adjunctive therapy of either a GLP-1 analog (exenatide), or a DPP-4 inhibitor (sitagliptin), given to a basal insulin analog (insulin glargine), and their effect on blood glucose control, versus insulin glargine alone as active comparator in type 2 diabetes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Due to the different mechanisms of action of the long-acting insulin analog insulin glargine and both a GLP-1 analog (exenatide) and a DPP-4-inhibitor (sitagliptin), it could be a promising approach to combine insulin glargine with either exenatide or sitagliptin for optimum control of fasting and postprandial blood glucose values. Thus, in the present study the influence of either exenatide or sitagliptin as a 4-week adjunctive therapy to a basal insulin (insulin glargine) was investigated versus insulin glargine alone as active comparator in subjects with type 2 diabetes. Preexisting metformin was continued, sulfonylureas, if any, were stopped. In particular, the effects on postprandial blood glucose excursion following ingestion of a standard breakfast, assessed after 4 weeks of treatment, the effects on mean daily blood glucose, on self-measured 7-point profiles, the percentage of subjects reaching ADA treatment goals (HbA1c < 7.0%) at the end of treatment, on fasting lipid profile, on HOMA index, weight, hypoglycemic episodes and general safety were assessed. The study consisted of a screening visit, a 4-8 week (depending on pre-treatment) run-in period, a 4-week treatment period, and a follow-up visit. There were weekly visits at the site and twice weekly telephone contacts.

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 1

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

  • Germany
      • Neuss, Germany, 41460
        • Profil Institut für Stoffwechselforschung GmbH

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

35 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • male or female subjects aged between 35 and 70 years, inclusive
  • type 2 diabetes with duration >6 months and <10 years
  • for at least 3 months: treatment solely with a long- or intermediate-acting insulin formulation (insulin glargine, insulin detemir, or NPH insulin) with or without a stable dose of metformin or treatment solely with a stable dose of metformin or combination of stable doses of metformin plus sulfonylureas
  • HbA1c >=7.0% and <=10.0%
  • if treated with antihypertensive or lipid lowering agents, the treatment regimen had to be stable during 3 months prior to study start
  • written informed consent

Exclusion Criteria:

  • history or presence of cancer or any clinically relevant diseases
  • chronic heart failure NYHA class III or IV, unstable angina pectoris or myocardial infarction within the previous 6 months
  • recurrent hypoglycemia
  • abnormal lab tests at screening (ALAT and/or ASAT >=3 times ULN), creatinine >1.6 mg/dL in males and >1.4 mg/dL in females
  • clinically relevant ECG findings at screening
  • treatment with a rapid-acting insulin or with a mixed insulin formulation during the previous 3 months
  • treatment with any other OHA than metformin or metformin plus sulfonylureas during the previous 3 months
  • any systemic or topical treatment with drugs known to influence glucose metabolism

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: insulin glargine + exenatide + metformin
Drug: insulin glargine + exenatide + preexisting metformin
insulin glargine once daily subcutaneously over 4 weeks, dose adjustment according to a treat-to-target algorithm, exenatide 5ug twice daily subcutaneously for 2 weeks, then 10ug twice daily for 2 weeks, continuation of preexisting metformin
Other Names:
  • Byetta
  • Lantus
Experimental: Insulin glargine + sitagliptin + metformin
Drug: insulin glargine + sitagliptin + preexisting metformin
insulin glargine once daily subcutaneously over 4 weeks, dose adjustment according to a treat-to-target algorithm, sitagliptin 100 mg once daily in the morning over 4 weeks, continuation of preexisting metformin
Other Names:
  • Januvia
  • Lantus
Active Comparator: insulin glargine + metformin
Drug: insulin glargine + preexisting metformin
insulin glargine once daily subcutaneously over 4 weeks, continuation of preexisting metformin
Other Names:
  • Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
the unadjusted 6-hour postprandial blood glucose excursion (AUCBG0-6h) following ingestion of a standardized breakfast
Time Frame: after 4 weeks of treatment
after 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
mean daily blood glucose (BG) from 7-point 24h BG profiles, fasting BG, self-measured 7-point BG profiles, percentage of subjects achieving ADA HbA1c treatment goals, fasting lipid profiles, HOMA-IR index, hypoglycemic episodes
Time Frame: after 4 weeks of treatment
after 4 weeks of treatment

Collaborators and Investigators

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

Sponsor

Profil Institut für Stoffwechselforschung GmbH

Collaborators

Sanofi

Investigators

  • Principal Investigator: Sabine Arnolds, MD, Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany

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

January 1, 2008

Primary Completion (Actual)

September 1, 2008

Study Completion (Actual)

November 1, 2008

Study Registration Dates

First Submitted

September 3, 2009

First Submitted That Met QC Criteria

September 3, 2009

First Posted (Estimate)

September 4, 2009

Study Record Updates

Last Update Posted (Estimate)

September 4, 2009

Last Update Submitted That Met QC Criteria

September 3, 2009

Last Verified

September 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 49/0316-Adjunct

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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