Metformin is an oral hypoglycemic agent used in non-insulin dependent diabetes. It has also been used for ovulation induction in PCOS. The popularity of metformin has waxed and waned over the years as different research studies have supported or disproven its efficacy.

A 2003 Cochrane review concluded that metformin should be a first-line fertility treatment for women with PCOS, citing improved ovulation rates and insulin parameters. A subsequent head-to-head comparison of metformin with clomiphene citrate reported similar ovulation and pregnancy rates, but fewer miscarriages with metformin (Palomba et. al., JCEM, 2005). In 2007, Legro et. al. published a large, randomized controlled trial in the NEJM that is considered to be the best evidence to date on this topic. In a comparison of clomiphene citrate + placebo, metformin + placebo and clomiphene citrate + metformin, the live birth rate was lowest in the metformin only group. There was no difference in live birth rates between the group taking only clomiphene citrate and clomiphene citrate + metformin. There were significantly more multiple pregnancies in the groups taking clomiphene citrate. As it currently stands, metformin is therefore not commonly used first-line for ovulation induction without a specific indication for its use. It is sometimes used as an adjunctive treatment with other fertility medications.

The dose of metformin for augmentation of ovulation induction is typically 1500 – 2000mg/day. Side effects include diarrhea, stomach upset, flatulence, abdominal discomfort and headache. It is excreted renally and the half-life is 4 – 8 hours.