Metformin hydrochloride, hereafter metformin, is a medication that doctors prescribe to treat type 2 diabetes, a condition where the body fails to respond effectively to the hormone insulin, leading to high blood sugar levels. In 1922, Emil Werner and James Bell, chemists working at Trinity College in Dublin, Ireland, were among the first to synthesize a compound with metformin’s modern chemical formula, namely dimethylbiguanide. At first, physicians didn’t recognize the compound’s ability to lower high blood sugar levels. However, the drug found other uses: physicians prescribed it to treat malaria and flu in the 1940s. Metformin as a treatment for diabetes became popular in the 1990s. In addition to type 2 diabetes, physicians also prescribe metformin to those with polycystic ovary syndrome, or PCOS, as some of its symptoms are similar to those of diabetes. Treating PCOS helps to reduce infertility caused by irregular or no ovulation. Metformin’s wide range of uses has helped hundreds of millions of people across the globe in managing diabetes, but also in treating PCOS and malaria.

In 1998, physician John E. Nestler and colleagues published “Effects of Metformin on Spontaneous and Clomiphene-Induced Ovulation in the Polycystic Ovary Syndrome,” hereafter “Metformin,” in the New England Journal of Medicine. Polycystic ovary syndrome, or PCOS, is an endocrine, or hormone-related, disorder that affects one in ten women of reproductive age, is characterized by symptoms such as an irregular menstrual cycle and high androgen levels, and can lead to infertility, or the inability to become pregnant. In the article, the authors report on the results of a randomized control trial they conducted in which they administered the insulin-lowering medication metformin to a group of thirty-five obese infertile female patients with PCOS, and compared them to twenty-six women receiving a placebo to see if metformin could improve spontaneous or drug-induced ovulation rates. They found that it could. As of 2026, “Metformin” is one of the most cited articles supporting metformin’s usage as a second-line treatment for infertility in women with PCOS.