28/07/2025
Metformin, an oral antihyperglycemic drug, acts as an insulin sensitiser and is used in certain clinical situations related to polycystic o***y syndrome (PCOS) and gestational diabetes mellitus. Although many studies and randomised clinical trials have not been able to clearly establish its superiority over alternative treatments for PCOS, metformin continues to be a useful and effective treatment option in specific subgroups of women either alone or as an adjunct with other therapies in management of PCOS.
It will be nearly 10 years since we wrote a narrative review on the role of metformin in management of clinical conditions related to women’s health. It still appears relevant and in my opinion, metformin remains underutilised in clinical settings related to PCOS.
What are the practical uses of metformin in the clinic? It appears to be a useful medical option which often improves regularity of menstrual bleeds and ovulations in women with PCOS (especially high BMI and wishing to conceive). Metformin also forms one of the management options in women who need anti-androgen therapy without the need for contraception at the same time (mild effect though). Women with PCOS undergoing in vitro fertilisation are likely to benefit from metformin therapy to reduce their risk of ovarian hyperstimulation syndrome. Metformin alone or in combination with insulin has been reported to have similar safety and efficacy to insulin for the treatment of GDM. There is ongoing research whether long-term metformin may be associated with a decreased risk of developing cancers like endometrial cancer in certain groups of patients but we need to wait for data to emerge.
https://journals.lww.com/obgynsurvey/abstract/2016/05000/role_of_metformin_in_women_s_health__review_of_its.20.aspx
What about metformin and risk of miscarriage in women with PCOS?
Here is a useful recent systematic review and meta-analysis from Cheshire et al. which explored the effects of preconception and first-trimester metformin use on pregnancy outcomes in women PCOS.
A total of 12 trustworthy studies (involving 1708 women) were included in the meta-analysis, all of which were graded low to moderate quality. Women who received preconception metformin that was continued throughout the first trimester of pregnancy showed higher clinical pregnancy rates (odds ratio, 1.57 [95% confidence interval, 1.11–2.23]), a possible reduction in miscarriage (odds ratio, 0.64 [95% confidence interval, 0.32–1.25]), and possible increase in live birth (odds ratio, 1.24 [95% confidence interval, 0.59–2.61]) than women who received either a placebo or no treatment.
Women who stopped metformin once pregnant not only had an increase in clinical pregnancy rate (odds ratio, 1.35 [95% confidence interval, 1.01–1.80]) but also had an indication of an increase in miscarriage rate (odds ratio, 1.46 [95% confidence interval, 0.73–2.90]) compared with those who received a placebo or no treatment.
The strengths of this review included the inclusion of RCTs, several of which were multi-centre. The main limitation of this review was the heterogeneous nature of the population studied and overall low quality of evidence with some results not reaching statistical certainty.
The authors concluded that continuing metformin treatment throughout the first trimester of pregnancy may reduce the risk of miscarriage and increase live birth rates in women with PCOS and highlighted the need for further high-quality research.
https://www.ajog.org/article/S0002-9378(25)00365-5/fulltext