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Drugs 2005; 65 (11): 1593-1594 0012-6667/05/0011-1593/$39.95/0 © 2005 Adis Data Information BV. All rights reserved.

Rosiglitazone/Metformin A Viewpoint by William L. Isley Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA

The inclusion of two drugs in one pill is generally a sign of patent protection, with some catering to patient convenience and, at least in the US, a reduced number of co-payments for prescriptions. Rarely, if ever, are such products a real therapeutic advance. Such is the case for Avandamet® 1. My only use of this product is for the patient who asks for a reduced number of co-payments and has a reason to be on the two drugs separately. What about the use of the two drugs in patients with type 2 diabetes mellitus? Metformin may have cardiovascular protective effects in obese patients, but contradictory findings in diverse populations suggest caution against unbridled enthusiasm. The author hypothesises that such contradictions may be related to the concomitant use of high-dose (glibenclamide) glyburide which is notorious for producing non-physiological insulin release and hypoglycaemia. Rosiglitazone has numerous beneficial ef-

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fects on inflammation and vasculature, and may preserve β-cell function to some degree, but its association with fluid retention (including congestive heart failure in patients with normal cardiac function and the development of macular edema) and fat weight gain (a few kilograms common, >10kg not uncommon) is highly problematic in some patients, particularly (though not always) those being treated with insulin secretagogues or insulin. The coadministration of the anorexia-inducing drug metformin probably blunts some of the weight gain. If the most beneficial effects of this drug combination were actually to occur in patients without the untoward effects of rosiglitazone, then this pill would be expected to produce numerous salutatory metabolic and vascular effects that would reduce the burden of disease. However, in the real world of patients, this is often not the case. Unless the biochemists can ultimately separate most of the beneficial effects of peroxisome proliferator-activated receptor-γ activation from the troublesome adverse effects, this therapy may be of dubious advantage. ▲

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