Impact of insulin sensitisation on metabolic and fertility outcomes in women with polycystic ovary syndrome and overweight or obesity - a systematic review, meta-analysis, and meta-regression

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. This systematic review, meta-analysis and meta-regression aims to compare the effect of insulin sensitiser pharmacotherapy on metabolic and reproductive outcomes in women with PCOS and overweight or obesity. We searched online databases MEDLINE via OVID, EMBASE, Clinicaltrials.gov and EudraCT for trials published from inception to 13th November 2023. Inclusion criteria were double-blind, randomised controlled trials in women diagnosed with PCOS, body mass index (BMI) ≥ 25 kg/m2, which reported metabolic or reproductive outcomes. The intervention was insulin sensitisation pharmacotherapy versus placebo or other agents. The primary outcomes were the changes from baseline BMI, fasting blood glucose and menstrual frequency. Nineteen studies were included in this review. Metformin had the most significant effect on the fasting plasma glucose and body mass index. Insulin sensitiser pharmacotherapy significantly reduced fasting plasma glucose, body mass index, fasting serum insulin, HOMA-IR, sex hormone binding globulin and total testosterone, but the effect size was small. There was a lack of menstrual frequency and live birth data. The results indicate a role for insulin sensitisers in improving the metabolic and, to a lesser degree, reproductive profile in these women. Further research should examine insulin sensitisers' effects on objective measures of fecundity