Exenatide Versus Glimepiride in Patients With Type 2 Diabetes

Overview

This study assesses the effects of twice-daily subcutaneous injection exenatide versus treatment with sulfonylurea (glimepiride) on long-term glycemic control and beta-cell function.

Full Title of Study: “Long Term Treatment With Exenatide Versus Glimepiride in Patients With Type 2 Diabetes Pretreated With Metformin (EUREXA: European Exenatide Study)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 2011

Interventions

  • Drug: exenatide
    • subcutaneous injection (5mcg or 10mcg), twice a day
  • Drug: glimepiride
    • oral tablet (titrated to maximally tolerated dose), once daily

Arms, Groups and Cohorts

  • Experimental: Exenatide
  • Active Comparator: Glimepiride

Clinical Trial Outcome Measures

Primary Measures

  • Number of Patients With Treatment Failure
    • Time Frame: Baseline to end of Period II (up to 4.5 years)
    • Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.
  • Time to Treatment Failure
    • Time Frame: Baseline to end of Period II (up to 4.5 years)
    • Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.

Secondary Measures

  • Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3
    • Time Frame: Year 3 in Period II
    • HOMA-B at Year 3. HOMA-B is an index of beta-cell function and was calculated as: HOMA-B = (20 x fasting insulin (measured in pmol/L))/((fasting glucose (measured in mmol/L) – 3.5) x 7.175).
  • Change in HOMA-B From Baseline to Endpoint
    • Time Frame: Baseline, end of Period II (up to 4.5 years)
    • Change in HOMA-B from baseline to endpoint.
  • Fasting Proinsulin/Insulin Ratio at Year 3
    • Time Frame: Year 3 in Period II
    • Fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio at Year 3.
  • Change in Fasting Proinsulin/Insulin Ratio From Baseline to Endpoint.
    • Time Frame: Baseline, end of Period II (up to 4.5 years)
    • Change in fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio from baseline to endpoint.
  • Ratio of the 30 Minute Increment in Plasma Insulin Concentration and the 30 Minute Increment in Plasma Glucose During the Oral Glucose Tolerance Test (DI30/DG30 Ratio) at Year 3
    • Time Frame: Year 3 in Period II
    • DI30/DG30 at Year 3. DI30/DG30 ratio was calculated as (30 minute post prandial insulin – fasting insulin) (measured in pmol/L)/(30 minute post prandial glucose – fasting glucose) (measured in mmol/L).
  • Change in DI30/DG30 Ratio From Baseline to Endpoint
    • Time Frame: Baseline, end of Period II (up to 4.5 years)
    • Change in DI30/DG30 ratio from baseline to endpoint.
  • Disposition Index at Year 3
    • Time Frame: Year 3 in Period II
    • Disposition Index at Year 3. Disposition index was calculated as (DI30/DG30 ratio)/(HOMA index for insulin resistance (HOMA-IR)); where HOMA-IR=(fasting insulin (measured in pmol/L) x fasting glucose (measured in mmol/L))/(22.5 x 7.175).
  • Change in Disposition Index From Baseline to Endpoint
    • Time Frame: Baseline, end of Period II (up to 4.5 years)
    • Change in disposition index from baseline to endpoint.
  • Change in HbA1c From Baseline to Year 3
    • Time Frame: Baseline, Year 3 in Period II
    • Change in HbA1c from baseline to Year 3.
  • Change in HbA1c From Baseline to Endpoint
    • Time Frame: Baseline, end of Period II (up to 4.5 years)
    • Change in HbA1c from baseline to endpoint. Endpoint for HbA1c was defined as the HbA1c measured at the treatment failure for patients reaching primary endpoint and was the last observation in study period II for other patients (either followed until the end of the study period II or discontinuing the study).
  • Fasting Plasma Glucose at Year 3
    • Time Frame: Year 3 in Period II
    • Fasting plasma glucose at Year 3.
  • Change in Fasting Plasma Glucose From Baseline to Endpoint
    • Time Frame: Baseline, end of Period II (up to 4.5 years)
    • Change in fasting plasma glucose from baseline to endpoint.
  • Postprandial (2 Hours) Plasma Glucose at Year 3
    • Time Frame: Year 3 in Period II
    • Postprandial (2 hours) plasma glucose at Year 3.
  • Change in Postprandial (2 Hours) Plasma Glucose From Baseline to Endpoint
    • Time Frame: Baseline, end of Period II (up to 4.5 years)
    • Change from baseline in postprandial (2 hours) plasma glucose to endpoint.
  • Change in Body Weight From Baseline to Year 3
    • Time Frame: Baseline, Year 3 in Period II
    • Change in Body weight from baseline to Year 3.
  • Systolic Blood Pressure at Year 3
    • Time Frame: Year 3 in Period II
    • Systolic Blood pressure at Year 3.
  • Diastolic Blood Pressure at Year 3
    • Time Frame: Year 3 in Period II
    • Diastolic Blood pressure at Year 3.
  • Heart Rate at Year 3
    • Time Frame: Year 3 in Period II
    • Heart rate at Year 3.
  • Triglycerides at Year 3
    • Time Frame: Year 3 in Period II
    • Triglycerides at Year 3.
  • Total Cholesterol at Year 3
    • Time Frame: Year 3 in Period II
    • Total Cholesterol at Year 3.
  • High-density Lipoprotein (HDL) Cholesterol at Year 3
    • Time Frame: Year 3 in Period II
    • HDL Cholesterol at Year 3.
  • Hypoglycemia Rate Per Year
    • Time Frame: Baseline to end of Period II (up to 4.5 years)
    • All hypoglycemia episodes were taken into account. Severe hypoglycemia: event requiring assistance of another person to administer carbohydrate, glucagons, or other resuscitative actions; Documented symptomatic hypoglycemia: event with typical symptoms accompanied by a measured plasma glucose concentration <=70 mg/dL; Asymptomatic hypoglycemia: event not accompanied by typical symptoms but with a measured plasma glucose concentration <=70 mg/dL; Probable symptomatic hypoglycemia: event with symptoms not accompanied by a plasma glucose determination.
  • Change in HbA1c From Baseline to Year 2 for Patients Randomized at Entry in Period III
    • Time Frame: Baseline in Period III, Year 2 in Period III
    • Change in HbA1c from baseline to Year 2.
  • Change in HbA1c From Baseline to Year 2 for Patients Not Randomized at Entry in Period III
    • Time Frame: Baseline in Period III, Year 2 in Period III
    • Change in HbA1c from baseline to Year 2.
  • Hypoglycemia Rate Per Year in Period III
    • Time Frame: Start of Period III to end of study
    • All hypoglycemia episodes were taken into account. Severe hypoglycemia: event requiring assistance of another person to administer carbohydrate, glucagons, or other resuscitative actions; Documented symptomatic hypoglycemia: event with typical symptoms accompanied by a measured plasma glucose concentration <=70 mg/dL; Asymptomatic hypoglycemia: event not accompanied by typical symptoms but with a measured plasma glucose concentration <=70 mg/dL; Probable symptomatic hypoglycemia: event with symptoms not accompanied by a plasma glucose determination.

Participating in This Clinical Trial

Inclusion Criteria

  • Diagnosed with type 2 diabetes mellitus. – Treated with diet and exercise and a stable, maximally tolerated dose of metformin for at least 3 months prior to screening. – HbA1c >=6.5% and <=9.0%. – Body Mass Index (BMI) >=25 kg/m^2 and <40 kg/m^2. Exclusion Criteria:

  • Participated in an interventional medical, surgical, or pharmaceutical study within 30 days prior to screening. – Characteristics contraindicating metformin or glimepiride use. – Receiving drugs that directly affect gastrointestinal motility. – Receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy. – Have used any prescription drug to promote weight loss within 3 months prior to screening. – Treated for longer than 2 weeks with any of the following medications within 3 months prior to screening: *insulin; *thiazolidinediones; *alpha-glucosidase inhibitors; *sulfonylurea; *meglitinides

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 85 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)
    • James Malone, MD, Study Director, Eli Lilly and Company

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