Effect of Exenatide Plus Metformin vs. Insulin Aspart Plus Metformin on Glycemic Control and Hypoglycemia in Patients With Type 2 Diabetes

Overview

This study in Germany is designed to compare the effects of twice-daily exenatide plus metformin and twice-daily premixed human insulin aspart plus metformin with respect to glycemic control, as measured by HbA1c, combined with the percentage of patients with at least one treatment-emergent hypoglycemic episode. Patients will be treated with study therapy for approximately 26 weeks.

Full Title of Study: “Effect of Exenatide Plus Metformin vs. Premixed Human Insulin Aspart Plus Metformin on Glycemic Control and Hypoglycemia in Patients With Inadequate Control of Type 2 Diabetes on Oral Antidiabetic Treatment”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 2009

Interventions

  • Drug: exenatide twice daily (BID)
    • subcutaneous injection (5 mcg or 10 mcg), twice a day
  • Drug: premixed insulin aspart twice daily (BID)
    • subcutaneous injection (titrated appropriately), twice a day

Arms, Groups and Cohorts

  • Experimental: Exenatide Twice Daily (BID)
  • Active Comparator: Premixed Insulin Aspart Twice Daily (BID)

Clinical Trial Outcome Measures

Primary Measures

  • Change in Glycosylated Hemoglobin (HbA1c)
    • Time Frame: Baseline and 26 weeks
    • Change in HbA1c from baseline after 26 weeks of treatment (i.e., HbA1c at week 26 minus HbA1c at week 0)
  • Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode)
    • Time Frame: 26 weeks
    • Risk for first hypoglycemic episode (blood glucose <=3.9 mmol/L or severe episode) to occur up to week 26

Secondary Measures

  • Percentage of Subjects Achieving HbA1c Target of < 6.5%
    • Time Frame: 26 weeks
    • Percentage of subjects achieving HbA1c target of < 6.5% at the end of study (week 26) [i.e., number of subjects who achieved HbA1c < 6.5% divided by total number of subjects times 100%].
  • Percentage of Subjects Achieving HbA1c Target of < 7.0%
    • Time Frame: 26 weeks
    • Percentage of subjects achieving HbA1c target of < 7.0% at the end of study (week 26) [i.e., number of subjects who achieved HbA1c < 7.0% divided by total number of subjects times 100%].
  • Incidence of Hypoglycemic Episodes [Blood Glucose <= 3.0 mmol/L or Severe] (Percentage of Subjects Who Experienced at Least One Treatment-emergent Hypoglycemic Episode During the 26-week Treatment Period)
    • Time Frame: 26 weeks
    • Risk for the first hypoglycemic episode to occur up to Week 26 (percentage of subjects who experienced at least one treatment-emergent hypoglycemic episode during the 26-week treatment period)[ i.e., number of subjects experiencing at least one hypoglycemic episode divided by total number of subjects times 100%]
  • Incidence of Nocturnal Hypoglycemia (Percentage of Subjects Who Experienced at Least One Episode of Nocturnal Hypoglycemia During the 26 Week Treatment Period)
    • Time Frame: 26 weeks
    • Risk for first nocturnal (night-time) hypoglycemic episode to occur up to week 26 (percentage of subjects who experienced at least one episode of nocturnal hypoglycemia during the 26 week treatment period) [i.e., number of subjects who experienced nocturnal hypoglycemia divided by total number of subjects times 100%].
  • 7 Point Self-monitored Blood Glucose (SMBG) Profiles
    • Time Frame: Baseline and 26 weeks
    • 7-point self-monitored blood glucose profiles at baseline and the end of the study, measured at 7 times during the day (pre-breakfast, 2 hours post-breakfast, pre-lunch, 2 hours post-lunch, pre-dinner, 2 hours post-dinner, and 3:00am).
  • Blood Lipid Levels
    • Time Frame: Baseline and 26 weeks
    • Total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol (calculated), and triglyceride levels at baseline (week 0) and the end of the study (week 26)
  • Change in Body Weight
    • Time Frame: Baseline and 26 weeks
    • Change in body weight from baseline after 26 weeks of treatment (i.e., body weight at week 26 minus body weight at week 0)
  • Change in Body Mass Index (BMI)
    • Time Frame: Baseline and 26 weeks
    • Change in BMI from baseline after 26 weeks of treatment (i.e., BMI at week 26 minus BMI at week 0)
  • Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ)
    • Time Frame: Baseline and 26 weeks
    • Total DTSQ treatment satisfaction score at baseline (week 0) and after 26 weeks of treatment (LOCF). Total DTSQ treatment satisfaction score is derived as sum score of the individual components 1 and 4-8 of the DTSQ questionnaire. Each component is scored on a scale of 0 (worst case) to 6 (best case). Higher values represent higher treatment satisfaction.
  • Patient Reported Outcomes: Quality of Life (SF-12)
    • Time Frame: Baseline and 26 weeks
    • SF-12 Physical and Mental Component Summary Scores at baseline (week 0) and after 26 weeks of treatment (LOCF). SF-12 Physical and Mental Component Summary Scores are normalized scores ranging from 0 (worst case) to 100 (best case), and are derived from responses to 12 questions. Scores > 50 indicate an above-average health status.

Participating in This Clinical Trial

Inclusion Criteria

  • Have been treated with diet and exercise and a stable, maximally tolerated dose of immediate-release or extended-release metformin, or the combination of metformin (any dosage) with sulfonylurea/meglitinides for at least 3 months prior to study start
  • Have not received thiazolidinediones, or alpha-glucosidase inhibitors for longer than 2 weeks within 3 months prior to study start, and have not received any insulin formulation for more than 14 days (other than in emergency situations) and within 14 days prior to study start
  • Have an HbA1c between 6.5% and 10.0%, inclusive
  • Have a body mass index (BMI) between 25 kg/m^2 and 40 kg/m^2, inclusive

Exclusion Criteria

  • Have type 1 diabetes or known latent autoimmune diabetes in adults
  • Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks prior to study start
  • Are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility (e.g., metoclopramide, cisapride, and chronic macrolide antibiotics)
  • Have used any prescription drug to promote weight loss within 3 months prior to study start
  • Have received treatment within 30 days prior to study start with a drug that has not received regulatory approval for any indication at the time of study entry
  • Have previously completed or withdrawn from this study or any other study investigating exenatide or GLP-1 analogs

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 90 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • AstraZeneca
  • Collaborator
    • Eli Lilly and Company
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Chief Medical Officer, MD, Study Director, Eli Lilly and Company

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