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Exenatide Versus Glimepiride in Patients With Type 2 Diabetes

Phase 3
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Registration Number
NCT00359762
Lead Sponsor
AstraZeneca
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1029
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Exenatideexenatide-
Glimepirideglimepiride-
Primary Outcome Measures
NameTimeMethod
Number of Patients With Treatment FailureBaseline 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 FailureBaseline 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 Outcome Measures
NameTimeMethod
Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3Year 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 DI30/DG30 Ratio From Baseline to EndpointBaseline, end of Period II (up to 4.5 years)

Change in DI30/DG30 ratio from baseline to endpoint.

Disposition Index at Year 3Year 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).

Triglycerides at Year 3Year 3 in Period II

Triglycerides at Year 3.

Total Cholesterol at Year 3Year 3 in Period II

Total Cholesterol at Year 3.

High-density Lipoprotein (HDL) Cholesterol at Year 3Year 3 in Period II

HDL Cholesterol at Year 3.

Hypoglycemia Rate Per YearBaseline 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 IIIBaseline 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 IIIBaseline in Period III, Year 2 in Period III

Change in HbA1c from baseline to Year 2.

Hypoglycemia Rate Per Year in Period IIIStart 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.

Change in HOMA-B From Baseline to EndpointBaseline, end of Period II (up to 4.5 years)

Change in HOMA-B from baseline to endpoint.

Fasting Proinsulin/Insulin Ratio at Year 3Year 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.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 3Year 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 Disposition Index From Baseline to EndpointBaseline, end of Period II (up to 4.5 years)

Change in disposition index from baseline to endpoint.

Change in HbA1c From Baseline to Year 3Baseline, Year 3 in Period II

Change in HbA1c from baseline to Year 3.

Change in HbA1c From Baseline to EndpointBaseline, 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 3Year 3 in Period II

Fasting plasma glucose at Year 3.

Change in Fasting Plasma Glucose From Baseline to EndpointBaseline, 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 3Year 3 in Period II

Postprandial (2 hours) plasma glucose at Year 3.

Change in Postprandial (2 Hours) Plasma Glucose From Baseline to EndpointBaseline, 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 3Baseline, Year 3 in Period II

Change in Body weight from baseline to Year 3.

Systolic Blood Pressure at Year 3Year 3 in Period II

Systolic Blood pressure at Year 3.

Diastolic Blood Pressure at Year 3Year 3 in Period II

Diastolic Blood pressure at Year 3.

Heart Rate at Year 3Year 3 in Period II

Heart rate at Year 3.

Trial Locations

Locations (1)

Research Site

🇬🇧

Wiltshire, United Kingdom

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