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Effects of Exenatide and Insulin Glargine in Subjects With Type 2 Diabetes

Phase 3
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Registration Number
NCT00097500
Lead Sponsor
AstraZeneca
Brief Summary

This Phase 3, open-label, multicenter study is designed to compare the effects of exenatide and insulin glargine (Lantus® injection) on beta-cell function in patients with type 2 diabetes mellitus using metformin.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
69
Inclusion Criteria
  • Diagnosis of type 2 diabetes, but otherwise healthy
  • HbA1c between 6.6% and 9.5%, inclusive.
  • Body mass index (BMI) of 25 kg/m2 to 40 kg/m2, inclusive.
  • Treated with a stable dose of metformin for at least 2 months prior to screening.
Exclusion Criteria
  • Patients previously in a study using exenatide.
  • Treated with oral anti-diabetic medications other than metformin within 2 months of screening (thiazolidinediones within 5 months of screening).
  • Treated with insulin within 3 months of screening.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Exenatide ArmMetforminExenatide and Metformin
Insulin Glargine ArmInsulin glargineInsulin Glargine and Metformin
Insulin Glargine ArmMetforminInsulin Glargine and Metformin
Exenatide ArmexenatideExenatide and Metformin
Primary Outcome Measures
NameTimeMethod
Beta-cell Function After 52 Weeks of TherapyBaseline (week -2) and 52 weeks

Treatment effect on beta-cell function as measured by the ratio of Week 52 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period \[i.e., clamp time 290 min to 300 min\]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 52 divided by arginine-stimulated insulin secretion at baseline \[week -2\]).

Secondary Outcome Measures
NameTimeMethod
Change in Second Phase C-peptide Releasebaseline (-2 weeks), 52 weeks, and 56 weeks

Ratio of second phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to second phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline \[week -2\]). C-peptide is measured as a surrogate marker of insulin secretion. Second phase C-peptide/insulin release is measured from time=10 minutes to time=80 minutes of glucose infusion during a hyperglycemic clamp procedure.

Beta-cell Function 4 Weeks After Cessation of TherapyBaseline (week -2) and 56 weeks

Treatment effect on beta-cell function as measured by the ratio of Week 56 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period \[i.e., clamp time 290 min to 300 min\]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 56 divided by arginine-stimulated insulin secretion at baseline \[week -2\]).

Change in First Phase C-peptide Releasebaseline (week -2), 52 weeks, and 56 weeks

Ratio of first phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to first phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline \[week -2\]). C-peptide is measured as a surrogate marker of insulin secretion. First phase C-peptide/insulin release is measured during the first ten minutes of glucose infusion during a hyperglycemic clamp procedure.

Change in Glycosylated Hemoglobin (HbA1c)Week 0 and week 52

Change in HbA1c from week 0 to week 52 (i.e., HbA1c at week 52 minus HbA1c at week 0).

Seven Point Self Monitored Blood Glucose (SMBG) Measurements0 weeks and 52 weeks

SMBG measured at 7 time points (before and after breakfast, before and after lunch, before and after dinner, at bedtime).

M-value at Baseline, Week 52 and Week 56baseline (week -2), 52 weeks, and 56 weeks

M-value at baseline (week -2), week 52 (end of on-drug period), and week 56 (during off-drug period). Insulin sensitivity was assessed during the euglycemic/hyperglycemic clamp test at baseline (week -2), week 52, and week 56. Insulin-mediated glucose uptake (M-value) was calculated as the mean glucose requirement during the 90-120 minute interval of the clamp.

Change in Fasting Plasma Glucose0 weeks and 52 weeks

Change in fasting plasma glucose from week 0 to week 52 (i.e., fasting plasma glucose at week 52 minus fasting plasma glucose at week 0).

Change in Body Weight0 weeks and 52 weeks

Change in body weight from week 0 to week 52 (i.e., body weight at week 52 minus body weight at week 0).

Trial Locations

Locations (1)

Research Site

🇸🇪

Goteborg, Sweden

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