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

Condition(s) targeted: Type 2 Diabetes

Intervention: rosiglitazone-metformin (Drug); Metformin (Drug); metformin+ gliclazide (Drug)

Phase: Phase 4

Status: Active, not recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, MD, Study Chair, Affiliation: GlaxoSmithKline

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.

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 design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Beta-cell function is reflected by insulin response. Evolution of insulin secretion capacity will be assessed over 3 years, by using clamp tests and meal tests before treatment and after 18 and 36 months of treatment

Evolution of insulin secretion capacity over 3 years measured by using clamp tests and meal tests before treatment and after 18 and 36 months of treatment (or in case of early withdrawal).

1st phase insulin secretion (during the 10 first minutes) : AUC, incremental AUC and peak value

2nd phase insulin secretion (AUC from 120 to 180 minutes and incremental AUC)

Insulin sensitivity : M/I (M = Metabolized glucose, I = Insulin) from 120 to 180 minutes

(The ratio M/I is a measure of the quantity of glucose metabolized per unit of plasma insulin concentration and is thus a reasonable index of tissue sensitivity to insulin).

Arginin test (peak value, AUC and incremental AUC) from 180 to 210 minutes.

Meal test (Sustacal): peak value of insulin and AUC over 3 hours.

Secondary outcome:

insulin secretion and sensitivity at baseline,M18 and 36. HbA1c ( glycosylated haemoglobin) at baseline ,M18 and 36. C peptide at baseline, M18 and 36

HOMA: % insulin secretion and sensitivity, performed before each stimulatory test

Centralised HbA1c, C-peptide at 0, 18 and 36 months or in case of early withdrawal.

Even if clinical efficacy is not the objective of the study, the following parameters, which are essential to evaluate glycaemic control of the patients and safety

(hypoglycemia+++) to adapt the treatment over the 3 year period, will be studied as a reference for the main evaluation and an evidence of compliance and/or of a possible therapeutic failure :

Local FPG, HbA1c every 3 months (except when clamp test) and in case of early withdrawal Adverse events every 3 months and in case of early withdrawal.

Minimum age: 40 Years. Maximum age: 75 Years. Gender(s): Both.

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

GSK Clinical Trials Call Center, Art Sur Meurthe 54510, France

GSK Clinical Trials Call Center, Bully Les Mines 62160, France

GSK Clinical Trials Call Center, Chartres 28000, France

GSK Clinical Trials Call Center, Chatenois 88170, France

GSK Clinical Trials Call Center, Colmar 68000, France

GSK Clinical Trials Call Center, Colombey Les Belles 54170, France

GSK Clinical Trials Call Center, Cugnaux 31270, France

GSK Clinical Trials Call Center, Dommartin Les Toul 54200, France

GSK Clinical Trials Call Center, Epinal 88000, France

GSK Clinical Trials Call Center, Evreux 27000, France

GSK Clinical Trials Call Center, Fenouillet 31150, France

GSK Clinical Trials Call Center, Bischheim 67800, France

GSK Clinical Trials Call Center, Blotzheim 68730, France

GSK Clinical Trials Call Center, Nantes 44100, France

GSK Clinical Trials Call Center, Toulouse 31100, France

GSK Clinical Trials Call Center, Albens 73410, France

GSK Clinical Trials Call Center, Marseille 13006, France

GSK Clinical Trials Call Center, Caen 14000, France

GSK Clinical Trials Call Center, Oinville 78250, France

GSK Clinical Trials Call Center, Paris 75011, France

GSK Clinical Trials Call Center, Versailles 78000, France

GSK Clinical Trials Call Center, La Chapelle Sur Erdre 44240, France

GSK Clinical Trials Call Center, Grand Quevilly 76120, France

GSK Clinical Trials Call Center, Gieres 38610, France

GSK Clinical Trials Call Center, Meulan 78250, France

GSK Clinical Trials Call Center, Nantes 44300, France

GSK Clinical Trials Call Center, Nantes 44000, France

GSK Clinical Trials Call Center, Cernay 68700, France

GSK Clinical Trials Call Center, Chambery 73000, France

GSK Clinical Trials Call Center, Champagne en Valromey 1200, France

GSK Clinical Trials Call Center, Strasbourg 67000, France

GSK Clinical Trials Call Center, Strasbourg cedex 67091, France

GSK Clinical Trials Call Center, Tours 37044, France

GSK Clinical Trials Call Center, Tours 37000, France

GSK Clinical Trials Call Center, Tours 37100, France

GSK Clinical Trials Call Center, Ville 67220, France

GSK Clinical Trials Call Center, Villemonble 93250, France

GSK Clinical Trials Call Center, Castelnaudary 11400, France

GSK Clinical Trials Call Center, Cergy 95800, France

GSK Clinical Trials Call Center, Dessenheim 68000, France

GSK Clinical Trials Call Center, Nantes cedex 01 44093, France

GSK Clinical Trials Call Center, Nogent Le Roi 28210, France

GSK Clinical Trials Call Center, Paris 75020, France

GSK Clinical Trials Call Center, Paris 75018, France

GSK Clinical Trials Call Center, Seraincourt 95450, France

GSK Clinical Trials Call Center, Soultz 68360, France

GSK Clinical Trials Call Center, St Pierre De Chandieu 69780, France

GSK Clinical Trials Call Center, Tours 37100, France

GSK Clinical Trials Call Center, Behren Les Forbach 57460, France

GSK Clinical Trials Call Center, Labarthe Sur Leze 31860, France

GSK Clinical Trials Call Center, Arras 62000, France

GSK Clinical Trials Call Center, Broglie 27270, France

GSK Clinical Trials Call Center, Gresy Sur Aix 73100, France

GSK Clinical Trials Call Center, Hanches 28130, France

GSK Clinical Trials Call Center, Les Sorinieres 44840, France

GSK Clinical Trials Call Center, Lille Cedex 59037, France

GSK Clinical Trials Call Center, Limoge en Quercy 46260, France

GSK Clinical Trials Call Center, Louviers 27400, France

GSK Clinical Trials Call Center, Luce 28100, France

GSK Clinical Trials Call Center, Luynes 37230, France

GSK Clinical Trials Call Center, Maintenon 28130, France

GSK Clinical Trials Call Center, Margon 28400, France

GSK Clinical Trials Call Center, Marseille Cedex 9 13274, France

GSK Clinical Trials Call Center, Montreuil 93100, France

GSK Clinical Trials Call Center, Husseren-Wesserling 68470, France

GSK Clinical Trials Call Center, Kunheim 68320, France

GSK Clinical Trials Call Center, Labarthe Sur Leze 31860, France

GSK Clinical Trials Call Center, Labastidette 31600, France

GSK Clinical Trials Call Center, Laxou 54520, France

GSK Clinical Trials Call Center, Paris cedex 10 75475, France

GSK Clinical Trials Call Center, Pinsaguel 31120, France

GSK Clinical Trials Call Center, Pont a Mousson 54700, France

GSK Clinical Trials Call Center, Reiningue 68950, France

GSK Clinical Trials Call Center, Romainville 93230, France

GSK Clinical Trials Call Center, Rouen 76100, France

GSK Clinical Trials Call Center, Rouen 76000, France

GSK Clinical Trials Call Center, Rouxmesnil-Bouteilles 76370, France

GSK Clinical Trials Call Center, Saint-Sebastien-sur-Loire 44230, France

GSK Clinical Trials Call Center, Moulins Les Metz 57160, France

GSK Clinical Trials Call Center, Mulhouse 68200, France

GSK Clinical Trials Call Center, Muret 31600, France

GSK Clinical Trials Call Center, Paris 75009, France

GSK Clinical Trials Call Center, Pulnoy 54425, France

GSK Clinical Trials Call Center, Rieumes 31870, France

GSK Clinical Trials Call Center, Saint Alban Leysse 73230, France

GSK Clinical Trials Call Center, Saint Cyr Sur Loire 37540, France

GSK Clinical Trials Call Center, Saint Etienne 42000, France

GSK Clinical Trials Call Center, Saint Jean 31240, France

GSK Clinical Trials Call Center, Saint Jean D'Arvey 73230, France

GSK Clinical Trials Call Center, Schiltigheim 67300, France

GSK Clinical Trials Call Center, Sercoeur 88600, France

GSK Clinical Trials Call Center, Villey-Saint Etienne 54200, France

GSK Clinical Trials Call Center, Voves 28150, France

GSK Clinical Trials Call Center, Wattrelos 59150, France

GSK Clinical Trials Call Center, Waziers 59119, France

GSK Clinical Trials Call Center, Wittenheim 68270, France

GSK Clinical Trials Call Center, Woippy 57140, France

GSK Clinical Trials Call Center, Lyon 69008, France

GSK Clinical Trials Call Center, Gieres 38610, France

GSK Clinical Trials Call Center, Toulouse 31300, France

GSK Clinical Trials Call Center, Bischheim 67800, France

GSK Clinical Trials Call Center, Belfort 9000, France

GSK Clinical Trials Call Center, Savonnieres 37510, France

GSK Clinical Trials Call Center, Vertou 44120, France

GSK Clinical Trials Call Center, Paris 75012, France

GSK Clinical Trials Call Center, Bretteville L'Orgueilleuse 14740, France

GSK Clinical Trials Call Center, Paris 75010, France

GSK Clinical Trials Call Center, Rambouillet 78120, France

Starting date: September 2004
Ending date: September 2008
Last updated: March 12, 2008