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    Drug Combo May Prevent Diabetes

    Study Shows Low Doses of Avandia, Metformin Ward Off Diabetes for at-Risk Patients

    Avandia: Safe at Any Dose? continued...

    Steven E. Nissen, MD, chairman of cardiovascular medicine at the Cleveland Clinic Foundation, was among the first to raise questions about Avandia's heart safety.

    "There is no evidence whatsoever that lower doses of [Avandia] are 'safe,'" Nissen tells WebMD via email. "Any suggestion that serious cardiovascular toxicity can be avoided by using a small dose represents pure speculation at best."

    Zinman agrees that his study enrolled too few patients, and was too short, to provide any information on Avandia's heart safety. However, he suggests that while it was not studied, Actos would likely have the same effect when combined with metformin in a low-dose combination.

    Mezitis agrees, but he'd like to see this supported by a clinical trial.

    "Yes, we can make the association that Actos would work the same way, but we don't have a study suggesting that," he says. "So I would feel more comfortable having a study first before recommending another medication."

    The Zinman trial was funded by GlaxoSmithKline, and Zinman reports receiving consulting fees, honoraria, and grant support from the company. However, he says the study was free of company influence and that the study investigators initiated the study, drew their conclusions, and published their findings without any company influence.

    Mezitis reports that he previously served on GlaxoSmithKline's speakers bureau but withdrew when issues about Avandia cardiovascular safety first arose.

    The Zinman study appears in the June 3 online edition of The Lancet.

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