Exenatide Versus Glimepiride in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00359762
First received: July 31, 2006
Last updated: June 6, 2014
Last verified: June 2014

July 31, 2006
June 6, 2014
September 2006
March 2011   (final data collection date for primary outcome measure)
  • Number of Patients With Treatment Failure [ Time Frame: Baseline to end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.
To test the hypothesis that exenatide injected twice daily is non-inferior to glimepiride given once-daily before breakfast to patients with type 2 diabetes.
Complete list of historical versions of study NCT00359762 on ClinicalTrials.gov Archive Site
  • Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    Change in HOMA-B from baseline to endpoint.
  • Fasting Proinsulin/Insulin Ratio at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    Change in DI30/DG30 ratio from baseline to endpoint.
  • Disposition Index at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    Change in disposition index from baseline to endpoint.
  • Change in HbA1c From Baseline to Year 3 [ Time Frame: Baseline, Year 3 in Period II ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    Change in fasting plasma glucose from baseline to endpoint.
  • Postprandial (2 Hours) Plasma Glucose at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Change in Body weight from baseline to Year 3.
  • Systolic Blood Pressure at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Systolic Blood pressure at Year 3.
  • Diastolic Blood Pressure at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Diastolic Blood pressure at Year 3.
  • Heart Rate at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Heart rate at Year 3.
  • Triglycerides at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Triglycerides at Year 3.
  • Total Cholesterol at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    Total Cholesterol at Year 3.
  • High-density Lipoprotein (HDL) Cholesterol at Year 3 [ Time Frame: Year 3 in Period II ] [ Designated as safety issue: No ]
    HDL Cholesterol at Year 3.
  • Hypoglycemia Rate Per Year [ Time Frame: Baseline to end of Period II (up to 4.5 years) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.
  • To compare the effects of exenatide and glimepiride on beta-cell function.
  • To compare the effects of exenatide and glimepiride on various pharmacodynamic measures.
  • To compare the safety and tolerability of exenatide and glimepiride.
  • To compare the effects of exenatide and glimepiride on the occurrence of hypoglycemic episodes.
  • To study the efficacy and safety of different treatment options.
Not Provided
Not Provided
 
Exenatide Versus Glimepiride in Patients With Type 2 Diabetes
Long Term Treatment With Exenatide Versus Glimepiride in Patients With Type 2 Diabetes Pretreated With Metformin (EUREXA: European Exenatide Study)

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • Drug: exenatide
    subcutaneous injection (5mcg or 10mcg), twice a day
    Other Name: Byetta
  • Drug: glimepiride
    oral tablet (titrated to maximally tolerated dose), once daily
    Other Name: Amaryl
  • Experimental: Exenatide
    Intervention: Drug: exenatide
  • Active Comparator: Glimepiride
    Intervention: Drug: glimepiride
Gallwitz B, Guzman J, Dotta F, Guerci B, Simó R, Basson BR, Festa A, Kiljański J, Sapin H, Trautmann M, Schernthaner G. Exenatide twice daily versus glimepiride for prevention of glycaemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA): an open-label, randomised controlled trial. Lancet. 2012 Jun 16;379(9833):2270-8. doi: 10.1016/S0140-6736(12)60479-6. Epub 2012 Jun 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1029
March 2011
March 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 85 Years
No
Contact information is only displayed when the study is recruiting subjects
Austria,   Czech Republic,   Finland,   France,   Germany,   Hungary,   Ireland,   Israel,   Italy,   Mexico,   Poland,   Spain,   Switzerland,   United Kingdom
 
NCT00359762
H8O-EW-GWBE
No
AstraZeneca
AstraZeneca
Eli Lilly and Company
Study Director: James Malone, MD Eli Lilly and Company
AstraZeneca
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP