Does treatment with rosiglitazone result in improved pancreatic beta-cell function as compared to glimepiride in metformin treated diabetes type 2 patients?

Study title:

Does treatment with rosiglitazon result in improved pancreatic ß-cell function as compared to glimepiride in metformin treated diabetes type 2 patients?



Introduction:

Thiazolidinediones, a new class of insulin sensitizing agents, have been shown to induce a shift of fat out of the visceral compartment – among which the pancreas – into the subcutaneous compartment. This could also result in a restoration or preservation of endogenous insulin secretion capacity, loss of which is one of the fundamental defects in Type 2 diabetes. A recent study could not confirm this hypothesis, but various shortcomings in the design of this previous study can be noted, most notably a treatment period that is likely to have been too short, and the fact that patients were not using metformin, the standard treatment for type 2 diabetes.



Aim of the study:

To investigate the effect of rosiglitazon treatment on -cell function in type 2 diabetes patients as compared to a sulfonylureumderivative, while both groups continue metformin treatment.



Design:

Twenty-two patients will be randomized to metformin with glimepiride 4 mg a day or metformin with rosiglitazon 8 mg a day.



Patients:

Eligible patients are those with Type 2 diabetes using metformin. Exclusion criteria are established coronary heart disease and previous use of a thiazolidinedione.



Measurements:

Patients will undergo a 200 min hyperglycaemic (aiming at 10 mmol/l) clamp with administration of glucagon-like peptide-1 (GLP-1) starting at 120 min (bolus injection of 4.5 pmol/kg followed by a continuous infusion of 1.5 pmol/kg/min until the end of the clamp) and an arginine (5 g) bolus at 180 min to elicit a further -cell response. Twenty-six weeks later, the assessments will be repeated, again on metformin, other study medication taken until the morning before this assessment.



Outcome measures:

Primary outcome measure will be the peak insulin concentrations during the hyperglycaemic clamp protocol.



Burden for the participants:

The risk for participants is judged to be minor. Participation mainly requires an investment of time and undergoing insertion of the sensors and blood sampling.



8-Aug-2007: trial has stopped because of stop cause problems with inclusion of patients.

By inducing a shift of fat out of the visceral compartment - among which the pancreas - into the subcutaneous compartment rosiglitazone results in improved pancreatic beta-cell function in type 2 diabetes patients, as compared to a sulfonylureumderivative, while both groups continue metformin treatment.

N/A

Patients will be randomized to 26 weeks of treatment with metformin with glimepiride 4 mg a day or metformin with rosiglitazone 8 mg a day.

Before the start of the treatment patients will undergo a 200 min. hyperglycaemic (aiming at 15 mmmol/l) clamp with administration of glucagon-like peptide-1 (GLP-1) starting at 120 min. and an arginine bolus at 180 min. to elicit a further beta-cell response.

Twenty-six weeks later, the assessments will be repeated, again on metformin, other study medication taken until the morning before this assessment.