Clinical trial NCT00367055: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Beta cell function
Type 2 diabetes
Combination treatment
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-08-22
Enrollment: 84
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Median Change From Baseline in the Insulin Secretory Capacity After a 36-month Treatment
timeFrame: Baseline and Month 36
Secondary outcomes:
measure: Median Change From Baseline in the Ratio M/I After a 36-month Treatment
timeFrame: Baseline and Month 36
measure: Median Change From Baseline in the Insulin Secretion Capacity After an 18-month Treatment
timeFrame: Baseline and Month 18
measure: Mean Change From Baseline in HbA1c at Month 36
timeFrame: Baseline and Month 36
measure: Mean Change From Baseline in FBG at Month 36
timeFrame: Baseline and Month 36
measure: Median Change From Baseline in Insulin Resistance Index (HOMA-IR) After a 36-month Treatment
timeFrame: Baseline and Month 36
measure: Median Change From Baseline in Beta Cell Function Index (HOMA-beta) After a 36-month Treatment
timeFrame: Baseline and Month 36
measure: Mean Change From Baseline in CPP Total and Incremental AUC T0-T30 After a 36-month Treatment
timeFrame: Baseline and Month 36
measure: Mean Change From Baseline in CPP Concentration Peak and Incremental Concentration Peak T0-T30 After a 36-month Treatment
timeFrame: Baseline and Month 36
measure: Mean Change From Baseline in Insulin Sensitivity Index at Months 18 and 36
timeFrame: Baseline and Months 18 and 36
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials, MD
role: STUDY_DIRECTOR
References: