Use of Antidiabetes Agents in the Treatment of PCOS and GDM

American Association of Diabetes Educators Breakout Session
Friday, August 13, 2004
2:00 PM - 3:00 PM

Polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) are usually diagnosed when the patient presents with hyperinsulinemia. PCOS is characterized by hyperinsulinemia, chronic anovulation, oligomenorrhea, and hyperandrogenism. The disease affects approximately 5% to 10% of women of reproductive age and is a common cause of infertility. GDM is diagnosed by any degree of glucose intolerance with onset or first recognition during pregnancy. Oral antidiabetes agents are not approved by the FDA for PCOS or GDM, and insulin is the drug of choice for these women. Recent studies have investigated whether lowering serum blood glucose levels with oral diabetes agents would help PCOS and GDM patients and whether the drugs are safe for the mother and fetus.

Metformin is a category B agent, which means it shows no risk to pregnant females in animal studies, but there have been no controlled studies in humans to confirm its safety. In several trials, including randomized controlled trials, investigators looked at whether metformin improved conception rates in women with PCOS. The majority of the studies indicate that metformin improves menstrual cyclicity, ovulation rates, and pregnancy rates in women with PCOS. Studies investigating the use of metformin to lower the risk of miscarriage in women with PCOS indicate that it decreases the rate of first-trimester spontaneous abortion in women with PCOS. It also appears that metformin decreases the rate of GDM in women with PCOS. No adverse fetal outcomes, congenital abnormalities, or fetal hypoglycemia were encountered, and at 6 months of age, all infants had normal motor and social development.

The thiazolidinediones rosiglitazone and pioglitazone are category C drugs, which means that animal studies show adverse effects, but there are no controlled studies in humans to confirm the drugs' effects. In a number of studies in which off-label use of thiazolidinediones (TZDs) were tested in improving outcomes in women with PCOS, they appear to be safe and effective. In women with GDM, a number of studies evaluated the efficacy and safety of TZDs in improving outcomes. Results have been somewhat mixed, though no adverse outcomes have been severe. It would appear that some antidiabetes agents may control glucose levels in some women with GDM, but long-range effects are unknown.