Rosiglitazone-Metformin Combination Versus Metformin-Sulfonylurea Combination On Beta-Cell Function In Type 2 Diabetes

Official Title: “Comparison of the Action of the Rosiglitazone-metformin Fixed-dose Combination and of a Metformin-sulfonylurea Free Combination on the B-cell Function in Type 2 Diabetic Patients Not Controlled With Metformin Alone.”

It has been shown in previous study that progressive glycemic deterioration was associated with progressive loss of b-cell function, measured by the decrease in plasma insulin levels, irrespective of the therapy used (diet, sulfonylureas or metformin).There is growing evidence that thiazolidinediones could have a positive action on the b-cell function. But it has not yet been demonstrated that they could protect from a deterioration in insulin secretion in the long term. So, it appears interesting to study the long term evolution of the b-cell function and the possible protection with rosiglitazone in patients with type 2 diabetes showing evidence of loss of b-cell function with metformin alone.

Intervention(s) in this Clinical Trial

• Drug: rosiglitazone-metformin
• Drug: Metformin
• Drug: metformin+ gliclazide

Primary Measures

• Median Change From Baseline in the Insulin Secretory Capacity After a 36-month Treatment
  • Time Frame: Baseline and Month 36
    Safety Issue?: No

Secondary Measures

• Median Change From Baseline in the Ratio M/I After a 36-month Treatment
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Median Change From Baseline in the Insulin Secretion Capacity After an 18-month Treatment
  • Time Frame: Baseline and Month 18
    Safety Issue?: No
• Mean Change From Baseline in HbA1c at Month 36
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Mean Change From Baseline in FBG at Month 36
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Median Change From Baseline in Insulin Resistance Index (HOMA-IR) After a 36-month Treatment
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Median Change From Baseline in Beta Cell Function Index (HOMA-beta) After a 36-month Treatment
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Mean Change From Baseline in CPP Total and Incremental AUC T0-T30 After a 36-month Treatment
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Mean Change From Baseline in CPP Concentration Peak and Incremental Concentration Peak T0-T30 After a 36-month Treatment
  • Time Frame: Baseline and Month 36
    Safety Issue?: No
• Mean Change From Baseline in Insulin Sensitivity Index at Months 18 and 36
  • Time Frame: Baseline and Months 18 and 36
    Safety Issue?: No

INCLUSION CRITERIA:

• Males and females 40 to 75 years of age (inclusive at the time of screening)
• Type 2 diabetes mellitus as defined by the WHO criteria, diagnosed for at least 1 year
• Subjects receiving 1.5 to 3g of metformin alone at a constant dose for at least 8 weeks prior to visit 1
• Patients with 6.5% < HbA1c > 8% at visit 1 and visit 2
• 25 < BMI < 35

EXCLUSION CRITERIA:

• Patient with type 1 diabetes
• Treatment with other hypoglycaemic agents than metformin in the last 3 months
• FPG >200 mg/dL at visit 2
• Hypersensitivity to the studied treatments (rosiglitazone, metformin chlorhydrate, gliclazide)
• Congestive heart failure (NYHA class I to IV), unstable or severe angina, recent myocardial infarction
• Respiratory insufficiency
• Subjects who have required the use of insulin for glycaemic control in the past 6 months prior to visit 1 (except during pregnancy or acute episodes such as hospitalization, trauma or infection) or subjects with a history of metabolic acidosis including diabetic ketoacidosis
• Anemia defined by haemoglobin concentration <11.0 g/dL for males and <10.0 g/dL for females
• Renal disease or renal dysfunction, e.g. as suggested by serum creatinine levels
• ≥135.0 µmol/L in males and ≥110.0 µmol/L in females and/or creatinine clearance <40 mL/min
• Presence of clinically significant hepatic disease, with ALT, AST, total bilirubin, alkaline phosphatase >2.5 times the upper limit of the normal reference range
• Subjects with chronic diseases requiring periodic ot intermittent treatment with oral or IV corticosteroids
• Subjects receiving danazol, miconazole or phenylbutazone
• Active alcohol, drug or medication abuse within the last 6 months or any condition that would indicate the likelihood of poor subject compliance
• Women who are lactating, pregnant or planning to become pregnant
• Any clinically significant abnormality identified at screening which, in the investigator's judgement, makes the subject unsuitable for inclusion in the study
• Use of any other investigational agent within 30 days or 5 half-lives (whichever is longer) prior to visit 1
• Subjects who receive or anticipate receiving radiocontrast dye during the study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: GlaxoSmithKline Industry

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials, MD Study Director GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00367055

Study ID Number: 101765

ClinicalTrials.gov Identifier: NCT00367055

Health Authority: France: National Consultative Ethics Committee for Health and Life Sciences