Exenatide Versus Glimepiride in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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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.

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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: exenatide
* Drug: glimepiride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide<br> | Drug: exenatide<br>* subcutaneous injection (5mcg or 10mcg), twice a day<br>* Other names: Byetta;|
| Active Comparator: Glimepiride<br> | Drug: glimepiride<br>* oral tablet (titrated to maximally tolerated dose), once daily<br>* Other names: Amaryl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Treatment Failure | 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. | Baseline to end of Period II (up to 4.5 years) | 
| Time to Treatment Failure | 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. | Baseline to end of Period II (up to 4.5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3 | 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). | Year 3 in Period II | 
| Change in HOMA-B From Baseline to Endpoint | Change in HOMA-B from baseline to endpoint. | Baseline, end of Period II (up to 4.5 years) | 
| Fasting Proinsulin/Insulin Ratio at Year 3 | Fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio at Year 3. | Year 3 in Period II | 
| Change in Fasting Proinsulin/Insulin Ratio From Baseline to Endpoint. | Change in fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio from baseline to endpoint. | Baseline, end of Period II (up to 4.5 years) | 
| 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 | 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). | Year 3 in Period II | 
| Change in DI30/DG30 Ratio From Baseline to Endpoint | Change in DI30/DG30 ratio from baseline to endpoint. | Baseline, end of Period II (up to 4.5 years) | 
| Disposition Index at Year 3 | 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). | Year 3 in Period II | 
| Change in Disposition Index From Baseline to Endpoint | Change in disposition index from baseline to endpoint. | Baseline, end of Period II (up to 4.5 years) | 
| Change in HbA1c From Baseline to Year 3 | Change in HbA1c from baseline to Year 3. | Baseline, Year 3 in Period II | 
| Change in HbA1c From Baseline to Endpoint | 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). | Baseline, end of Period II (up to 4.5 years) | 
| Fasting Plasma Glucose at Year 3 | Fasting plasma glucose at Year 3. | Year 3 in Period II | 
| Change in Fasting Plasma Glucose From Baseline to Endpoint | Change in fasting plasma glucose from baseline to endpoint. | Baseline, end of Period II (up to 4.5 years) | 
| Postprandial (2 Hours) Plasma Glucose at Year 3 | Postprandial (2 hours) plasma glucose at Year 3. | Year 3 in Period II | 
| Change in Postprandial (2 Hours) Plasma Glucose From Baseline to Endpoint | Change from baseline in postprandial (2 hours) plasma glucose to endpoint. | Baseline, end of Period II (up to 4.5 years) | 
| Change in Body Weight From Baseline to Year 3 | Change in Body weight from baseline to Year 3. | Baseline, Year 3 in Period II | 
| Systolic Blood Pressure at Year 3 | Systolic Blood pressure at Year 3. | Year 3 in Period II | 
| Diastolic Blood Pressure at Year 3 | Diastolic Blood pressure at Year 3. | Year 3 in Period II | 
| Heart Rate at Year 3 | Heart rate at Year 3. | Year 3 in Period II | 
| Triglycerides at Year 3 | Triglycerides at Year 3. | Year 3 in Period II | 
| Total Cholesterol at Year 3 | Total Cholesterol at Year 3. | Year 3 in Period II | 
| High-density Lipoprotein (HDL) Cholesterol at Year 3 | HDL Cholesterol at Year 3. | Year 3 in Period II | 
| Hypoglycemia Rate Per Year | 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. | Baseline to end of Period II (up to 4.5 years) | 
| Change in HbA1c From Baseline to Year 2 for Patients Randomized at Entry in Period III | Change in HbA1c from baseline to Year 2. | Baseline in Period III, Year 2 in Period III | 
| Change in HbA1c From Baseline to Year 2 for Patients Not Randomized at Entry in Period III | Change in HbA1c from baseline to Year 2. | Baseline in Period III, Year 2 in Period III | 
| Hypoglycemia Rate Per Year in Period III | 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. | Start of Period III to end of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exenatide, diabetes, Amylin, Lilly, glimepiride