Women with polycystic ovary syndrome, now renamed polyendocrine metabolic ovarian syndrome (PMOS), who were taking a GLP-1 drug before they conceived had 62% fewer adverse pregnancy outcomes over two years than matched women taking metformin, according to a large health-record study published on 10 October in the Journal of Clinical Endocrinology & Metabolism. It is an observational analysis, not a randomised trial, and its authors say plainly that it does not support taking these drugs during pregnancy.
How the comparison was built
A team at the University of Liverpool used TriNetX, a global network of electronic health records, to run what is called a target trial emulation: an analysis of routine records designed to mimic, as closely as records allow, the trial that was never run. It included women aged 18 or over with PCOS or PMOS who were prescribed liraglutide, semaglutide or tirzepatide before conception, and compared them with women prescribed metformin, a diabetes drug long used off-label in PCOS. The two groups were matched one-to-one on demographics, body measurements, other conditions and other medicines, leaving 48,126 women in each, or 96,252 in all.
The main outcome was a composite of adverse pregnancy outcomes over two years: hypertensive, glycaemic and placental complications, problems with delivery and labour, foetal growth problems, preterm birth and early pregnancy complications. The hazard ratio was 0.38, with a 95% confidence interval of 0.34 to 0.41. Put simply, the GLP-1 group had a rate of these outcomes about 62% lower than the metformin group, and the interval runs from 59% to 66% lower. That interval is narrow because the study is large, and narrowness says nothing about whether the comparison is free of bias.
Three secondary results were labelled exploratory. Individual pregnancy outcomes were also lower. Major adverse cardiovascular events had a hazard ratio of 0.88 (0.81 to 0.95), between 5% and 19% lower. New type 2 diabetes had a hazard ratio of 0.31 (0.30 to 0.33), about 69% lower. The abstract does not give absolute event rates, so these ratios cannot be turned into a number of women spared a complication.
Weight and insulin resistance before pregnancy are both linked to gestational diabetes and high blood pressure in pregnancy, and PMOS raises the risk of each. The authors read their result as consistent with the benefit of getting metabolic health in order before conception. Comparing against metformin, an active treatment rather than no treatment, makes that reading stronger than a comparison with untreated women would have been. It still cannot show the drugs caused the difference.
What the result does not change is the position on pregnancy itself. The current FDA labels for both Wegovy and Zepbound say weight loss offers no benefit to a pregnant patient and may cause foetal harm, cite animal studies showing risks to the foetus, and tell prescribers to discontinue the drug once a pregnancy is recognised. Both labels say human data are insufficient to establish a drug-related risk. The study does not test any of that: it measured women who used the drugs before conceiving. Our pages on semaglutide and tirzepatide set out what the approved labels cover.
What this cannot show
This is a records study, and records describe who was prescribed what, not why. Women prescribed newer and more expensive drugs may differ from those given metformin in ways matching cannot capture, including income, insurance and access to antenatal care. Outcomes recorded outside the network would be missed. The abstract does not say how the timing of drug use relative to conception was defined, nor whether women stopped before or after conceiving. The authors report that the associations varied across some sensitivity analyses without saying which. This report is based on the published abstract, which does not state the funding source. A randomised trial would be needed to show that starting a GLP-1 drug before a planned pregnancy changes outcomes.
Sources: Henney AE, Holmes PJ, Riley D, et al. Preconception incretin therapy reduces pregnancy and cardiometabolic outcomes in polycystic ovary syndrome. Journal of Clinical Endocrinology & Metabolism, published online 10 October 2026 (PubMed 42857939). FDA prescribing information, section 8.1 Pregnancy: Wegovy and Zepbound (label effective 28 August 2026).
