{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T10:51:03Z","timestamp":1791629463738,"version":"4.3.4"},"reference-count":0,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Polycystic ovary syndrome (PCOS), now polyendocrine metabolic ovarian syndrome (PMOS), is associated with reproductive and cardiometabolic complications. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonists (RAs) improve obesity-related outcomes, but their impact on pregnancy outcomes in PMOS remains unclear.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a target trial emulation using the TriNetX global federated health research network. Women \u226518 years with PCOS\/PMOS receiving pre-conception GLP-1\/dual GLP-1\/GIP RA therapy (liraglutide, semaglutide or tirzepatide) were compared with metformin. Propensity score matching (1:1) accounted for demographics, anthropometrics, comorbidities and medications. The primary outcome was a composite of adverse pregnancy outcomes (hypertensive, glycaemic, placental, delivery, labour, foetal growth, preterm and early pregnancy complications) over two years. Individual pregnancy endpoints, major adverse cardiovascular events (MACE) and type 2 diabetes (T2D) were exploratory secondary outcomes. Cox regression generated hazard ratios (HRs) and 95% confidence intervals (CIs).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n After matching, 48,126 patients were included per group. Pre-conception GLP-1\/GIP RA use was associated with lower risk of the composite pregnancy outcome (HR 0.38; 95% CI 0.34\u20130.41). Exploratory analyses also demonstrated lower risks of individual pregnancy endpoints, MACE (HR 0.88; 95% CI 0.81\u20130.95) and T2D (HR 0.31; 95% CI 0.30\u20130.33). Associations varied across some sensitivity analyses.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Pre-conception GLP-1\/GIP RA use in women with PCOS\/PMOS was associated with lower risks of adverse pregnancy outcomes and cardiometabolic disease compared with metformin, consistent with potential benefits of pre-conception metabolic optimisation. This study cannot evaluate in-pregnancy safety or efficacy, and these findings do not support GLP-1\/GIP RA use during gestation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/clinem\/dgag423","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:49:48Z","timestamp":1791546588000},"source":"Crossref","is-referenced-by-count":0,"title":["Preconception incretin therapy reduces pregnancy and cardiometabolic outcomes in polycystic ovary syndrome"],"prefix":"10.1210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-9470","authenticated-orcid":false,"given":"Alex E","family":"Henney","sequence":"first","affiliation":[{"name":"Department of Cardiovascular & Metabolic Medicine, University of Liverpool , Liverpool ,","place":["UK"]},{"name":"Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust , Liverpool, Merseyside ,","place":["UK"]},{"name":"Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust , Liverpool, Merseyside ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phoebe J","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular & Metabolic Medicine, University of Liverpool , Liverpool ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular & Metabolic Medicine, University of Liverpool , Liverpool ,","place":["UK"]},{"name":"Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust , Liverpool, Merseyside ,","place":["UK"]},{"name":"Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust , Liverpool, Merseyside ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Heague","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular & Metabolic Medicine, University of Liverpool , Liverpool ,","place":["UK"]},{"name":"Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust , Liverpool, Merseyside ,","place":["UK"]},{"name":"Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust , Liverpool, Merseyside ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharani K","family":"Hapangama","sequence":"additional","affiliation":[{"name":"Liverpool Women\u2019s NHS Foundation Trust, Crown Street Liverpool and Department of Women\u2019s Health, University of Liverpool , UK L8 7SS"},{"name":"NIHR Northwest coast Applied Research Collaboration"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uazman","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular & Metabolic Medicine, University of Liverpool , Liverpool ,","place":["UK"]},{"name":"Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust , Liverpool, Merseyside ,","place":["UK"]},{"name":"Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust , Liverpool, Merseyside ,","place":["UK"]},{"name":"Centre for Musculoskeletal Research, Faculty of Biology Medicine and Health, The University of Manchester , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6128-0822","authenticated-orcid":false,"given":"Daniel J","family":"Cuthbertson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular & Metabolic Medicine, University of Liverpool , Liverpool ,","place":["UK"]},{"name":"Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust , Liverpool, Merseyside ,","place":["UK"]},{"name":"Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust , Liverpool, Merseyside ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,10,10]]},"container-title":["The Journal of Clinical Endocrinology & Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag423\/71836626\/dgag423.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag423\/71836626\/dgag423.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T10:33:01Z","timestamp":1791628381000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article\/doi\/10.1210\/clinem\/dgag423\/8907155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,10]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgag423","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,10]]},"article-number":"dgag423"}}