{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:00:02Z","timestamp":1785506402269,"version":"3.56.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009448","name":"Universit\u00e0 degli Studi della Campania Luigi Vanvitelli","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009448","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Endocrine"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), used to treat type 2 diabetes and obesity, may improve metabolic health before conception. However, their association to hypertensive disorders of pregnancy (HDP) after periconceptional or early pregnancy exposure remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a meta-analysis to investigating association between GLP-1 RAs preconception or first trimester of gestation exposure and HDP risk. Cochrane Central Register of Controlled Trials databases, ClinicalTrials.gov, PubMed, Scopus, and EMBASE databases were searched from inception through December 15, 2025. All eligible studies were observational cohorts. Case reports, reviews, editorials, and studies that lacked HDP data were excluded. We pooled odds ratios with 95% confidence intervals using a random-effects Mantel\u2013Haenszel model. ROBINS-I tool was used to evaluate risk of bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 75 records identified, 3 retrospective cohort studies met inclusion criteria with 10,880 pregnancies (4942 exposed to GLP-1 RAs and 5938 unexposed). All the studies were conducted in the United States between 2014\u20132025 and evaluated the semaglutide, liraglutide, dulaglutide, tirzepatide, exenatide, lixisenatide, and albiglutide exposure. Two studies showed a lower HDP risks among exposed pregnant, whereas one study found a higher risk. In the pooled analysis, GLP-1 RA exposure showed a HDP risk with an OR 0.91 (OR 0.91, CI 0.57\u20131.47) with no statistical significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Periconceptional or first-trimester exposure to GLP-1 RAs are not significantly associated with HDP risk. This available evidence is limited and indicating the need for large prospective studies to establish a possible association between GLP-1 RAs are not significantly associated with HDP risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12020-026-04701-9","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T13:09:17Z","timestamp":1785503357000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypertensive disorders of pregnancy and GLP-1 receptor agonist timing: a systematic review and meta-analysis"],"prefix":"10.1007","volume":"91","author":[{"given":"Davide","family":"Pisani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Driul","family":"Lorenza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Fordellone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cerillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fatigati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Hanul\u00edkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Mariniello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"De Franciscis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Pasquini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6071-0245","authenticated-orcid":false,"given":"Marco","family":"La Verde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"issue":"3","key":"4701_CR1","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.bpobgyn.2014.10.002","volume":"29","author":"S Mitchell","year":"2015","unstructured":"S. Mitchell, D. Shaw, The worldwide epidemic of female obesity. Best. Pract. Res. Clin. Obstet. Gynaecol. 29(3), 289\u2013299 (2015)","journal-title":"Best. Pract. Res. Clin. Obstet. Gynaecol."},{"issue":"5","key":"4701_CR2","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1007\/s00404-024-07849-9","volume":"311","author":"SA Price","year":"2025","unstructured":"S.A. Price, A. Nankervis, Considering the use of GLP-1 receptor agonists in women with obesity prior to pregnancy: a narrative review. Arch. Gynecol. Obstet. 311(5), 1241\u20131247 (2025)","journal-title":"Arch. Gynecol. Obstet."},{"issue":"7","key":"4701_CR3","doi-asserted-by":"publisher","first-page":"e1004236","DOI":"10.1371\/journal.pmed.1004236","volume":"20","author":"AM Darling","year":"2023","unstructured":"A.M. Darling, D. Wang, N. Perumal, E. Liu, M. Wang, T. Ahmed, P. Christian, K.G. Dewey, G. Kac, S.H. Kennedy, Risk factors for inadequate and excessive gestational weight gain in 25 low-and middle-income countries: an individual-level participant meta-analysis. PLoS Med. 20(7), e1004236 (2023)","journal-title":"PLoS Med."},{"issue":"Suppl 3","key":"4701_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4755-11-S3-S3","volume":"11","author":"SV Dean","year":"2014","unstructured":"S.V. Dean, Z.S. Lassi, A.M. Imam, Z.A. Bhutta, Preconception care: nutritional risks and interventions. Reprod. Health 11(Suppl 3), S3 (2014)","journal-title":"Reprod. Health"},{"issue":"1","key":"4701_CR5","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s13300-018-0535-9","volume":"10","author":"I Romera","year":"2019","unstructured":"I. Romera, A. Cebri\u00e1n-Cuenca, F. \u00c1lvarez-Guisasola, F. Gomez-Peralta, J. Reviriego, A review of practical issues on the use of glucagon-like peptide-1 receptor agonists for the management of type 2 diabetes. Diabetes Ther. 10(1), 5\u201319 (2019)","journal-title":"Diabetes Ther."},{"issue":"6","key":"4701_CR6","doi-asserted-by":"publisher","first-page":"2821","DOI":"10.1007\/s12325-021-01710-0","volume":"38","author":"J Ard","year":"2021","unstructured":"J. Ard, A. Fitch, S. Fruh, L. Herman, Weight loss and maintenance related to the mechanism of action of glucagon-like peptide 1 receptor agonists. Adv. Ther. 38(6), 2821\u20132839 (2021)","journal-title":"Adv. Ther."},{"key":"4701_CR7","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1111\/dom.16364","volume":"27","author":"RW Thomsen","year":"2025","unstructured":"R.W. Thomsen, A. Mailhac, J.B. L\u00f8hde, A. Potteg\u00e5rd, Real\u2010world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP\u20101RA\u2010based weight\u2010loss therapies. Diabetes, Obes. Metab. 27, 66\u201388 (2025)","journal-title":"Diabetes, Obes. Metab."},{"issue":"4","key":"4701_CR8","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1093\/humupd\/dmz019","volume":"25","author":"M Jensterle","year":"2019","unstructured":"M. Jensterle, A. Janez, E. Fliers, J.H. DeVries, E. Vrtacnik-Bokal, S.E. Siegelaar, The role of glucagon-like peptide-1 in reproduction: from physiology to therapeutic perspective. Hum. Reprod. Update 25(4), 504\u2013517 (2019)","journal-title":"Hum. Reprod. Update"},{"issue":"1","key":"4701_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-023-01500-5","volume":"23","author":"L Zhou","year":"2023","unstructured":"L. Zhou, H. Qu, L. Yang, L. Shou, Effects of GLP1RAs on pregnancy rate and menstrual cyclicity in women with polycystic ovary syndrome: a meta-analysis and systematic review. BMC Endocr. Disord. 23(1), 245 (2023)","journal-title":"BMC Endocr. Disord."},{"issue":"1","key":"4701_CR10","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ajog.2024.08.024","volume":"232","author":"RF Drummond","year":"2025","unstructured":"R.F. Drummond, K.E. Seif, E.A. Reece, Glucagon-like peptide-1 receptor agonist use in pregnancy: a review. Am. J. Obstet. Gynecol. 232(1), 17\u201325 (2025)","journal-title":"Am. J. Obstet. Gynecol."},{"key":"4701_CR11","doi-asserted-by":"publisher","first-page":"123","DOI":"10.2147\/DMSO.S130834","volume":"10","author":"PA Levin","year":"2017","unstructured":"P.A. Levin, H. Nguyen, E.T. Wittbrodt, S.C. Kim, Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research. Diabetes, Metab. Syndr. Obes. 10, 123\u2013139 (2017)","journal-title":"Diabetes, Metab. Syndr. Obes."},{"issue":"4","key":"4701_CR12","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1007\/s42000-024-00541-2","volume":"23","author":"C Tsiampali","year":"2024","unstructured":"C. Tsiampali, I.D. Vachliotis, A. Goulas, S.A. Polyzos, Animal studies on glucagon-like peptide-1 receptor agonists and related polyagonists in nonalcoholic fatty liver disease. Hormones 23(4), 611\u2013619 (2024)","journal-title":"Hormones"},{"issue":"2","key":"4701_CR13","doi-asserted-by":"publisher","first-page":"100298","DOI":"10.1016\/j.clinme.2025.100298","volume":"25","author":"MS Varughese","year":"2025","unstructured":"M.S. Varughese, F. O\u2019Mahony, L. Varadhan, GLP-1 receptor agonist therapy and pregnancy: evolving and emerging evidence. Clin. Med. 25(2), 100298 (2025)","journal-title":"Clin. Med."},{"issue":"4","key":"4701_CR14","doi-asserted-by":"publisher","first-page":"e083550","DOI":"10.1136\/bmjopen-2023-083550","volume":"14","author":"K Dao","year":"2024","unstructured":"K. Dao, S. Shechtman, C. Weber-Schoendorfer, O. Diav-Citrin, R.H. Murad, M. Berlin, A. Hazan, J.L. Richardson, G. Eleftheriou, V. Rousson, Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services. BMJ Open. 14(4), e083550 (2024)","journal-title":"BMJ Open."},{"issue":"6","key":"4701_CR15","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.3390\/jcm9061980","volume":"9","author":"M Lewandowska","year":"2020","unstructured":"M. Lewandowska, B. Wi\u0119ckowska, S. Sajdak, Pre-pregnancy obesity, excessive gestational weight gain, and the risk of pregnancy-induced hypertension and gestational diabetes mellitus. J. Clin. Med. 9(6), 1980 (2020)","journal-title":"J. Clin. Med."},{"issue":"1","key":"4701_CR16","doi-asserted-by":"publisher","first-page":"5581570","DOI":"10.1155\/2021\/5581570","volume":"2021","author":"WN Phoswa","year":"2021","unstructured":"W.N. Phoswa, O.P. Khaliq, The role of oxidative stress in hypertensive disorders of pregnancy (preeclampsia, gestational hypertension) and metabolic disorder of pregnancy (gestational diabetes mellitus). Oxid. Med. Cell. Longev. 2021(1), 5581570 (2021)","journal-title":"Oxid. Med. Cell. Longev."},{"key":"4701_CR17","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.preghy.2021.03.001","volume":"24","author":"F Li","year":"2021","unstructured":"F. Li, T. Wang, L. Chen, S. Zhang, L. Chen, J. Qin, Adverse pregnancy outcomes among mothers with hypertensive disorders in pregnancy: a meta-analysis of cohort studies. Pregnancy Hypertens. 24, 107\u2013117 (2021)","journal-title":"Pregnancy Hypertens."},{"issue":"8","key":"4701_CR18","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.7150\/ijbs.59965","volume":"17","author":"X Ma","year":"2021","unstructured":"X. Ma, Z. Liu, I. Ilyas, P.J. Little, D. Kamato, A. Sahebka, Z. Chen, S. Luo, X. Zheng, J. Weng, GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential. Int. J. Biol. Sci. 17(8), 2050 (2021)","journal-title":"Int. J. Biol. Sci."},{"issue":"2","key":"4701_CR19","doi-asserted-by":"publisher","first-page":"116.e1","DOI":"10.1016\/j.ajog.2025.01.019","volume":"233","author":"MR Imbroane","year":"2025","unstructured":"M.R. Imbroane, F. LeMoine, C.T. Nau, Preconception glucagon-like peptide-1 receptor agonist use associated with decreased risk of adverse obstetrical outcomes. Am. J. Obstet. Gynecol. 233(2), 116.e1\u2013116.e7 (2025)","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"24","key":"4701_CR20","doi-asserted-by":"publisher","first-page":"2186","DOI":"10.1001\/jama.2025.20951","volume":"334","author":"J Maya","year":"2025","unstructured":"J. Maya, D. Pant, Y. Fu, K. James, C. Batlle, S. Hsu, D.C. Soria-Contreras, L.L. Shook, C. Mow, M.-F. Hivert, Gestational weight gain and pregnancy outcomes after GLP-1 receptor agonist discontinuation. JAMA 334(24), 2186\u20132196 (2025)","journal-title":"JAMA"},{"key":"4701_CR21","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1097\/AOG.0000000000005995","volume":"147","author":"N Pondugula","year":"2026","unstructured":"N. Pondugula, J.F. Culhane, L.S. Lundsberg, C. Partridge, A.A. Merriam, Gestational weight gain and hypertensive disorders of pregnancy with prepregnancy and early pregnancy glucagon-like peptide-1 receptor agonist exposure. Obstet. Gynecol. 147, 293\u2013302 (2026)","journal-title":"Obstet. Gynecol."},{"issue":"4","key":"4701_CR22","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1097\/HJH.0000000000004250","volume":"44","author":"A Malik","year":"2026","unstructured":"A. Malik, R.A. Malik, A new era in reducing obesity and the risk of cardiovascular disease events in preeclampsia. J. Hypertens. 44(4), 579\u2013580 (2026)","journal-title":"J. Hypertens."},{"issue":"6","key":"4701_CR23","doi-asserted-by":"publisher","first-page":"147916412312217","DOI":"10.1177\/14791641231221740","volume":"20","author":"M Evans","year":"2023","unstructured":"M. Evans, P. Kuodi, C.J. Akunna, N. McCreedy, M. Donsmark, H. Ren, C.A. Nnaji, Cardiovascular and renal outcomes of GLP-1 receptor agonists vs. DPP-4 inhibitors and basal insulin in type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Vasc. Dis. Res. 20(6), 14791641231221740 (2023)","journal-title":"Diabetes Vasc. Dis. Res."},{"issue":"1","key":"4701_CR24","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.bpa.2022.02.003","volume":"36","author":"E Overton","year":"2022","unstructured":"E. Overton, D. Tobes, A. Lee, Preeclampsia diagnosis and management. Best. Pract. Res. Clin. Anaesthesiol. 36(1), 107\u2013121 (2022)","journal-title":"Best. Pract. Res. Clin. Anaesthesiol."},{"issue":"1","key":"4701_CR25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0020-7292(02)80002-9","volume":"77","author":"Practice ACoO","year":"2002","unstructured":"Practice ACoO, ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int. J. Gynaecol. Obstet. 77(1), 67\u201375 (2002)","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"4701_CR26","doi-asserted-by":"publisher","first-page":"409","DOI":"10.3389\/fcimb.2019.00409","volume":"9","author":"J Wang","year":"2019","unstructured":"J. Wang, X. Gu, J. Yang, Y. Wei, Y. Zhao, Gut microbiota dysbiosis and increased plasma LPS and TMAO levels in patients with preeclampsia. Front. Cell. Infect. Microbiol. 9, 409 (2019)","journal-title":"Front. Cell. Infect. Microbiol."},{"issue":"2","key":"4701_CR27","doi-asserted-by":"publisher","first-page":"487","DOI":"10.2337\/dci19-0066","volume":"43","author":"JB Buse","year":"2020","unstructured":"J.B. Buse, D.J. Wexler, A. Tsapas, P. Rossing, G. Mingrone, C. Mathieu, D.A. D\u2019Alessio, M.J. Davies, 2019 update to: management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 43(2), 487\u2013493 (2020)","journal-title":"Diabetes Care"},{"issue":"8","key":"4701_CR28","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1111\/dom.14725","volume":"24","author":"JP Wilding","year":"2022","unstructured":"J.P. Wilding, R.L. Batterham, M. Davies, L.F. Van Gaal, K. Kandler, K. Konakli, I. Lingvay, B.M. McGowan, T.K. Oral, J. Rosenstock, Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes, Obes. Metab. 24(8), 1553\u20131564 (2022)","journal-title":"Diabetes, Obes. Metab."},{"key":"4701_CR29","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.preghy.2020.03.001","volume":"20","author":"AM Dude","year":"2020","unstructured":"A.M. Dude, M.A. Kominiarek, D.M. Haas, J. Iams, B.M. Mercer, S. Parry, U.M. Reddy, G. Saade, R.M. Silver, H. Simhan, Weight gain in early, mid, and late pregnancy and hypertensive disorders of pregnancy. Pregnancy Hypertens. 20, 50\u201355 (2020)","journal-title":"Pregnancy Hypertens."},{"issue":"1","key":"4701_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-017-1567-2","volume":"17","author":"Y Shao","year":"2017","unstructured":"Y. Shao, J. Qiu, H. Huang, B. Mao, W. Dai, X. He, H. Cui, X. Lin, L. Lv, D. Wang, Pre-pregnancy BMI, gestational weight gain and risk of preeclampsia: a birth cohort study in Lanzhou, China. BMC Pregnancy Childbirth 17(1), 400 (2017)","journal-title":"BMC Pregnancy Childbirth"}],"container-title":["Endocrine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-026-04701-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12020-026-04701-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-026-04701-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T13:09:19Z","timestamp":1785503359000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12020-026-04701-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4701"],"URL":"https:\/\/doi.org\/10.1007\/s12020-026-04701-9","relation":{},"ISSN":["1559-0100"],"issn-type":[{"value":"1559-0100","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]},"assertion":[{"value":"7 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The research protocol was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD420251273858).","order":1,"name":"Ethics","label":"Institutional review board statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interest.","order":2,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"241"}}