In a rare head-to-head study, rosiglitazone (Avandia) proved better than either metformin (Glucophage) or glyburide (Micronase) in controlling glucose levels in patients with newly diagnosed type 2 diabetes.

In an international trial, researchers enrolled 4,127 patients (aged 30-75 years) with fasting glucose levels of 126-180 mg/dL who had received no previous drug therapy for their condition. On a randomized basis, the patients were assigned to receive one of the three trial drugs and were followed for up to six years.

After five years, 15% of those on rosiglitazone had a fasting glucose level >180 mg/dL compared with 21% of those taking metformin and 34% of those receiving glyburide. Similar results occurred when the threshold was lowered to >140 mg/dL. Rosiglitazone had its greatest effect in older patients and those with large waist measurements. The researchers said the positive effects of the drug therapy resulted from a slowed rate of loss of beta-cell function and improved insulin sensitivity.

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As for side effects, the rosiglitazone and metformin patients suffered more cardiovascular events and heart failure than the glyburide patients, but both effects occurred infrequently in all three groups. Rosiglitazone caused more edema than the other drugs but fewer GI side effects than metformin and less hypoglycemia than glyburide. Both rosiglitazone and glyburide caused weight gain. A surprise effect of rosiglitazone was fracture of the humerus and hand in women.

The researchers concluded that “progressive loss of glycemic control can be delayed and a mean level of glycated hemoglobin maintained at <7% for a longer period with rosiglitazone (60 months) than with either metformin (45 months) or glyburide (33 months).” They said their findings also “confirm the value of metformin as an initial treatment and the greater efficacy of metformin than of glyburide” (N Engl J Med. 2006;355:2427-2443).

The study was sponsored by GlaxoSmithKline, the maker of Avandia.