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

July 20, 2010 updated by: GlaxoSmithKline

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.

Study Overview

Status

Completed

Conditions

Type 2 Diabetes Mellitus

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: TREATMENT
Allocation: RANDOMIZED
Interventional Model: PARALLEL
Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Change From Baseline in the Insulin Secretory Capacity After a 36-month Treatment Time Frame: Baseline and Month 36	Change from baseline in the insulin secretory capacity was measured by the assesment of blood insulin concentrations (conc.) using the hyperglycaemic clamp (HC) technique, per intravenous glucose perfusion by a catheter. Change from baseline for insulin conc peaks (highest conc level) was calculated as the Month 36 value minus the baseline value. Insulin secretion was assessed by calculating AUC during the first 10 minutes of HC (incremental and total AUC0-10 min) and the AUC after the first 10 minutes of the HC (10-180min).	Baseline and Month 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Change From Baseline in the Ratio M/I After a 36-month Treatment Time Frame: Baseline and Month 36		Baseline and Month 36
Median Change From Baseline in the Insulin Secretion Capacity After an 18-month Treatment Time Frame: Baseline and Month 18	Change from baseline was calculated as the Month 18 value minus the baseline value. Insulin secretion capacity is measured in blood (blood level of insulin) and is a response of the pancreatic beta-cells to hyperglycemia induced by a glucose IV bolus, then infusion. Hyperglycemic clamp (HC) is a reference technique to evaluate the initial and the secondary phases of insulin secretion.	Baseline and Month 18
Mean Change From Baseline in HbA1c at Month 36 Time Frame: Baseline and Month 36	Change from baseline was calculated as the Month 36 value minus the baseline value. HbA1c levels were measured by blood draw.	Baseline and Month 36
Mean Change From Baseline in FBG at Month 36 Time Frame: Baseline and Month 36	Change from baseline was calculated as the Month 36 value minus the baseline value. FBG levels were measured by blood draw.	Baseline and Month 36
Median Change From Baseline in Insulin Resistance Index (HOMA-IR) After a 36-month Treatment Time Frame: Baseline and Month 36		Baseline and Month 36
Median Change From Baseline in Beta Cell Function Index (HOMA-beta) After a 36-month Treatment Time Frame: Baseline and Month 36		Baseline and Month 36
Mean Change From Baseline in CPP Total and Incremental AUC T0-T30 After a 36-month Treatment Time Frame: Baseline and Month 36		Baseline and Month 36
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		Baseline and Month 36
Mean Change From Baseline in Insulin Sensitivity Index at Months 18 and 36 Time Frame: Baseline and Months 18 and 36	Change from baseline was calculated as the Month 18 and 36 values minus the baseline value. Insulin sensitivity is measured as the quantity of glucose metabolized per unit of plasma insulin concentration.	Baseline and Months 18 and 36

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2004

Primary Completion (ACTUAL)

October 1, 2008

Study Completion (ACTUAL)

October 1, 2008

Study Registration Dates

First Submitted

August 21, 2006

First Submitted That Met QC Criteria