Insulin Sensitizing Agents

Given the prevalence of insulin resistance seen in PCOS, a number of insulin-sensitizing agents have been studied in the treatment of symptoms. Currently metformin, a biguanide, and pioglitazone and rosiglitazone, thiazolidinediones, are available clinically, and all have been studied in PCOS. The single most common agent for use in PCOS is metformin. Metformin appears to work by reducing hepatic glucose output thereby reducing the demand for insulin. A meta-analysis of thirteen studies of metformin in PCOS concluded that metformin significantly enhanced the rate of ovulation. There was also evidence for improved insulin levels and reduced cholesterol. There is conflicting evidence that metformin's effects are partially mediated through weight reduction. Metformin has been noted in several studies to be associated with weight reduction in the initial phase of treatment, but this is not consistently seen. The effects of metformin on pregnancy loss and gesta-tional diabetes have been studied only in small uncontrolled trials. Current evidence is not sufficient to conclude a consistent positive effect.

The thiazolidinedione therapies are associated with improved insulin action at the level of skeletal muscle and liver. The largest available study involved troglitazone, which is no longer on the market due to hepatotoxicity. However, significant improvements in ovulation were noted in a 48-week trial. Both pioglitazone and rosiglitazone have been shown to improve ovulatory rates in PCOS in small trials. Both are pregnancy category C agents and have not been studied in pregnancy. No association with weight reduction is noted with these agents. Several studies indicate slight increases in weight with use although metabolic improvements are noted.

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