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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00971659
• Other study ID #: 49/0316-Adjunct
• Status: Completed
• Phase: Phase 1
• First received: September 3, 2009
• Last updated: September 3, 2009
• Start date: January 2008
• Est. completion date: November 2008

Study information

• Verified date: September 2009
• Source: Profil Institut für Stoffwechselforschung GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: November 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

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
• 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
• insulin glargine + preexisting metformin
insulin glargine once daily subcutaneously over 4 weeks, continuation of preexisting metformin

Locations

Country	Name	City	State
Germany	Profil Institut für Stoffwechselforschung GmbH	Neuss

Sponsors (2)

Lead Sponsor	Collaborator
Profil Institut für Stoffwechselforschung GmbH	Sanofi

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the unadjusted 6-hour postprandial blood glucose excursion (AUCBG0-6h) following ingestion of a standardized breakfast		after 4 weeks of treatment	No
Secondary	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		after 4 weeks of treatment	Yes