The effect of glucagon-like peptide-1 receptor agonists versus metformin on pregnancy rates in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized trials

Abstract

Background: PCOS-related infertility is closely linked to metabolic dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve insulin resistance and promote weight loss in women with PCOS, but their direct effect on reproductive outcomes remains uncertain. Objectives: To evaluate whether GLP-1RA-based therapy improves pregnancy outcomes in women with PCOS. Search strategy: PubMed, Scopus, and Web of Science were searched from inception to February 2026. Selection criteria: Randomized controlled trials comparing GLP-1RA-based therapy, alone or combined with metformin, with metformin monotherapy in women with PCOS. Data collection and analysis: Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2. Dichotomous outcomes were pooled as odds ratios with 95% confidence intervals using a random-effects model. Certainty of evidence was rated with GRADE, and trial sequential analysis was performed. Main results: Four reports from three randomized trials (252 participants) were included. GLP-1RA-based treatment did not significantly improve overall pregnancy (OR 1.41, 95% CI 0.81-2.45), but was associated with an increase in natural pregnancy (OR 3.10, 95% CI 1.74-5.49), with no significant effect on IVF pregnancy (OR 1.01, 95% CI 0.36-2.85). TSA supported the finding for natural pregnancy, while evidence for overall pregnancy remained underpowered. Certainty of evidence was moderate for natural pregnancy and low for the other outcomes. Conclusions: GLP-1 receptor agonists show promising preliminary signals for improving spontaneous conception in women with PCOS, but the available evidence remains limited. Current evidence is insufficient to draw conclusions regarding IVF outcomes. Larger trials with standardized endpoints, including live birth, are needed.