Rosiglitazone, a thiazolidinedione with a different side chain from those of troglitazone and pioglitazone, reduces plasma glucose levels and glucose production and increases glucose clearance in patients with type 2 diabetes mellitus. Insulin sensitivity, pancreatic beta-cell function and surrogate markers of cardiovascular risk factors are significantly improved by rosiglitazone. Double-blind trials of 8 to 26 weeks of rosiglitazone 4 or 8 mg/day monotherapy indicate significant decreases in fasting plasma glucose (-2 to -3 mmol/L with 8 mg/day) and glycosylated haemoglobin levels [HbA(1c); -0.6 to -0.7% (-0.8 to -1.1% in drug-naive patients) with 8 mg/day]. Significant decreases in hyperglycaemic markers occurred when rosiglitazone was combined with metformin (HbA(1c) -0.8 to -1.0%), a sulphonylurea (-1.4%) or insulin (-1.2%) for 26 weeks versus little change with active comparator monotherapy. Efficacy was maintained in trials of < or = 2 years, and was also apparent in various ethnic subgroups, elderly patients, and both obese and nonobese patients. Rosiglitazone is currently not indicated in combination with injected insulin. It should be administered in conjunction with diet and exercise regimens. Rosiglitazone is generally well tolerated. Despite rare individual reports of liver function abnormalities in rosiglitazone recipients, the incidence of these in clinical trials (< or = 2 years' duration) was similar to that in placebo and active comparator groups. Fluid retention associated with rosiglitazone may be the cause of the increased incidence of anaemia in clinical trials, and also means that patients should be monitored for signs of heart failure during therapy. Although bodyweight is increased overall with rosiglitazone therapy, increases are in subcutaneous, not visceral, fat; hepatic fat is decreased. The pharmacokinetic profile of rosiglitazone is not substantially altered by age or renal impairment, nor are there important drug interactions. Rosiglitazone is not indicated in patients with active liver disease or increased liver enzymes.
Conclusions: Oral rosiglitazone 4 or 8 mg/day provides significant antihyperglycaemic efficacy and is generally well tolerated, both as monotherapy and in combination with other antihyperglycaemic agents, in patients with type 2 diabetes mellitus who do not have active liver disease. Long-term data are required before conclusions can be drawn about the clinical significance of positive changes to surrogate markers of cardiovascular disease risk and improvements to pancreatic beta-cell function. Rosiglitazone significantly improves insulin sensitivity and, as such, is a welcome addition to the treatment options for patients with type 2 diabetes mellitus.