Metformin and rosiglitazone combination effective in treating type 2 diabetes
Från JAMA 2000;283:1695-1702.

In patients with type 2 diabetes whose disease is inadequately controlled with metformin alone, adjunct therapy with rosiglitazone improves glycemic control, insulin sensitivity, and beta-cell function.

    Rosiglitazone and metformin have different mechanisms of action, Dr. Vivian Fonseca of Tulane University in New Orleans, Louisiana, and a multicenter team explain in the April 5th issue of The Journal of the American Medical Association. To look at the effects of combination therapy in type 2 diabetes patients, the researchers randomized 348 patients to receive either metformin plus placebo or metformin plus one of two doses of rosiglitazone for 26 weeks.

    Patients receiving rosiglitazone had a significant decrease in levels of glycosylated hemoglobin compared with the control group. At the end of the study period, the absolute change in HbA1c was -0.56% in those receiving 4 mg/d rosiglitazone, -0.78% in the 8-mg/d group, and +0.45% in patients on metformin alone. In addition, 57.3% of patients receiving the higher dose of rosiglitazone reached a glycosylated hemoglobin level of 8%, which the authors note is below the American Diabetes Association action point. In contrast, 35.9% of patients receiving metformin plus placebo achieved the same level.

    Rosiglitazone also had significant effects on insulin sensitivity and beta-cell function, increasing homeostasis model assessment (HOMA)-S and HOMA-B values in a dose-dependent fashion compared with metformin plus placebo. Both doses of rosiglitazone resulted in increased body mass, while control patients had decreased body mass. In addition, rosiglitazone increased the levels of total and low-density lipoprotein cholesterol.

The frequency of adverse effects was similar across all groups.
- In patients whose fundamental abnormality is insulin resistance, such a combination raises the exciting possibility of treating diabetes by targeting the underlying cause of the disease, rather than the traditional approach of stimulating insulin secretion, Dr. Fonseca's group concludes.

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