A Cochrane review included 6 trials involving a total of 174 women. 4 trials compared metformin vs combined oral contraceptives (COC) (n=104) and 2 compared metformin + COC vs COC alone (n=70). Limited data demonstrated no evidence of difference in effect between metformin and COC on hirsutism and acne. There was either insufficient or no data on the relative efficacy of metformin or COC (alone or in combination) for preventing the development of diabetes, cardiovascular disease, or endometrial cancer. Metformin was less effective than COC in improving menstrual pattern (OR 0.08, 95% CI 0.01 to 0.45). Metformin resulted in a higher incidence of gastrointestinal (OR 7.75, 95% CI 1.32 to 45.71), and a lower incidence of non-gastrointestinal (OR 0.11, 95% CI 0.03 to 0.39), severe adverse effects requiring stopping of medication. Metformin was less effective in reducing serum androgen levels (total testosterone: weighted mean difference (WMD) 0.54, 95% CI 0.22 to 0.86; free androgen index: WMD 3.69, 95% CI 2.56 to 4.83). Metformin was more effective than COC in reducing fasting insulin (WMD -3.46, 95% CI -5.39 to -1.52) and not increasing triglyceride (WMD -0.48, 95% -0.86 to -0.09) levels, but there was insufficient evidence regarding comparative effects on reducing fasting glucose or cholesterol levels. There are no data comparing ISDs other than metformin (that is rosiglitazone, pioglitazone, and D-chiro-inositol) versus COC (alone or in combination).
Comment: The quality of evidence is downgraded by study quality (lack of blinding, inadequate intention-to-treat), by indirectness (differences in studied patients, short duration), and by imprecise results (few patients and wide confidence intervals).