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.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are getting a lot of attention in PCOS research circles. A new meta-analysis has put these research peptides head-to-head against metformin to see what actually moves the needle for pregnancy rates in women with polycystic ovary syndrome. Researchers pulled data from three randomized controlled trials, stacking up a total of 252 participants.
Eur J Obstet Gynecol Reprod Biol
by Kar E, Yeh J, Efe MA et al.
“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. Kar E(1), Yeh J(2), Efe MA(3), Çelik HG(4), Bozdağ G(5), Baştu E(6). Author information: (1)Department of Obstetrics and Gynecology, Hasköy State Hospital, Muş, Türkiye. Electronic address: emre.kar@sbu.edu.tr. (2)Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Harvard University, MA, USA. (3)Department of Obstetrics and Gynecology, Beylikduzu State Hospital, Istanbul, Turkey. (4)IVF and Endometriosis Center, Acibadem Fulya Hospital, Istanbul, 34349, Turkey; Department of Obstetrics and Gynecology, Acibadem University School of Medicine, Istanbul, Turkey. (5)IVF Center, Bahçeci Fulya, Istanbul, Turkey. (6)IVF and Endometriosis Center, Nesta Clinic, Istanbul, Turkey. 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. Copyright © 2026 Elsevier B.V. All rights reserved. Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.”
Here’s the core finding: GLP-1RA-based protocols didn’t make a statistically significant difference in overall pregnancy rates compared to metformin alone. But the story gets more interesting when you zoom in on natural, unassisted pregnancies. Women taking GLP-1RAs were over three times more likely to conceive naturally (odds ratio 3.10), while IVF pregnancy rates stayed flat. Translation: these peptides are showing real potential for spontaneous conception, at least in the short term.
Key takeaway:
GLP-1RAs may help women with PCOS get pregnant naturally — but the evidence for IVF outcomes isn’t there yet.
A few caveats. The studies reviewed were small, and the evidence certainty was only moderate for natural pregnancy (and low for everything else). The authors call for larger, better-designed trials to really nail down the effects — especially on live birth rates, not just conception.
For researchers tracking the intersection of peptides and reproductive health, this is a solid signal to keep GLP-1RAs on your radar. The field is wide open for more robust, standardized studies.
Curious about the latest in peptide research? Check the peptide research index for updates, or browse the vendor directory if you’re interested in sourcing research compounds. Peptide science keeps moving forward — and PCOS is firmly in the crosshairs.
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