Which Drug for Initial Treatment of Type 2 Diabetes?

Allan S. Brett, MD

Journal Watch. 2006;5(12) 

Summary and Comment

Rosiglitazone was moderately more effective than metformin or glyburide, but costs and adverse events must also be considered.


Clinicians usually prescribe metformin, a sulfonylurea, or a thiazolidinedione as initial drug therapy for type 2 diabetes. Researchers compared these options in a double-blind, randomized trial of rosiglitazone (Avandia), a thiazolidinedione.

The manufacturer-funded study involved 4360 adults with recently diagnosed type 2 diabetes and fasting plasma glucose levels of 126 to 180 mg/dL. Patients received rosiglitazone, metformin, or glyburide, with each drug started at low dose and titrated to the maximum dose, if necessary. Median treatment duration was 4 years.

The estimated 5-year incidence of treatment failure, defined as fasting plasma glucose exceeding 180 mg/dL, was significantly lower with rosiglitazone (15%) than with metformin (21%) or glyburide (34%). Adverse events were consistent with known side effects of the drugs. For example, congestive heart failure and weight gain occurred most commonly with rosiglitazone, gastrointestinal side effects with metformin, and hypoglycemia with glyburide. Rosiglitazone recipients had more edema and slightly higher LDL cholesterol levels than patients in the other two groups, and thus were more likely to receive prescriptions for diuretics and lipid-lowering drugs.


In this study, rosiglitazone was moderately more effective than the other two drugs in controlling fasting glucose levels during the first several years after diagnosis of type 2 diabetes. However, an editorialist believes that these results do not convincingly favor rosiglitazone when side effects and costs are considered. The editorialist is the lead author of a recently published consensus statement (cosponsored by the American Diabetes Association) that recommends metformin as the first-line drug (Diabetologia 2006; 49:1711-21).

—Allan S. Brett, MD

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