Clinical trial NCT00971659: Adjunctive Therapy of Exenatide or Sitagliptin to Insulin Glargine in Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes
Keywords: type 2 diabetes
Lead sponsor: Profil Institut für Stoffwechselforschung GmbH
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2009-09-04
Enrollment: 48
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: the unadjusted 6-hour postprandial blood glucose excursion (AUCBG0-6h) following ingestion of a standardized breakfast
timeFrame: after 4 weeks of treatment
Secondary outcomes:
measure: 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
timeFrame: after 4 weeks of treatment
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
Study officials:
affiliation: Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany
name: Sabine Arnolds, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Arnolds S, Dellweg S, Clair J, Dain MP, Nauck MA, Rave K, Kapitza C. Further improvement in postprandial glucose control with addition of exenatide or sitagliptin to combination therapy with insulin glargine and metformin: a proof-of-concept study. Diabetes Care. 2010 Jul;33(7):1509-15. doi: 10.2337/dc09-2191. Epub 2010 Mar 31.