{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:49:44Z","timestamp":1789778984280,"version":"4.0.1"},"reference-count":60,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZZYSM202211006"],"award-info":[{"award-number":["SZZYSM202211006"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Overweight or obese women with polycystic ovary syndrome (PCOS) often experience significant metabolic and hormonal disturbances. This systematic review and meta\u2010analysis evaluated whether liraglutide combined with metformin is more effective than metformin alone in improving glycaemic control, lipid metabolism, body mass index (BMI) and sex hormone profiles in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, Weipu, SinoMed and Wanfang Data for randomised controlled trials (RCTs) comparing liraglutide plus metformin to metformin monotherapy in overweight or obese women with PCOS. Primary outcomes included fasting plasma glucose (FPG), 2\u2010h postprandial glucose, HbA1c, fasting insulin, homeostasis model assessment of insulin resistance (HOMA\u2010IR), BMI, sex hormones (luteinising hormone [LH], follicle\u2010stimulating hormone [FSH], total testosterone [TT]) and lipid profiles (total cholesterol [TC], triglycerides [TG], low\u2010density lipoprotein cholesterol [LDL\u2010C] and high\u2010density lipoprotein cholesterol [HDL\u2010C]). Subgroup analyses were conducted by treatment duration, lifestyle intervention and baseline BMI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 19 RCTs involving 1657 women with PCOS were included. Compared to metformin alone, the combination of liraglutide and metformin significantly improved glycaemic metabolism: FPG (standard mean difference\u2009=\u2009\u22121.92, 95% confidence interval [CI] [\u22122.43, \u22121.41];\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200995%), 2\u2010h postprandial glucose (\u22122.87, [\u22123.70, \u22122.05]; 97%), HbA1c (\u22122.91, [\u22123.84, \u22121.98]; 96%), HOMA\u2010IR (\u22122.29, [\u22122.98, \u22121.60]; 97%) and fasting insulin (\u22120.75, [\u22121.41, \u22120.09]; 94%). BMI was also significantly reduced (\u22121.64, [\u22122.38, \u22120.89]; 97%). Hormonal indicators improved, including LH (\u22121.48, [\u22121.83, \u22121.14]; 85%), FSH (\u22121.17, [\u22121.62, \u22120.73]; 92%) and TT (\u22120.66, [\u22121.30, \u22120.03]; 95%). In terms of lipid metabolism, reductions were observed in TC (\u22122.34, [\u22123.67, \u22121.01]; 98%), TG (\u22120.58, [\u22120.96, \u22120.21]; 79%) and LDL\u2010C (\u22120.79, [\u22121.36, \u22120.22]; 91%), while HDL\u2010C increased (0.67, [0.21, 1.13]; 83%). Longer treatment duration (\u226516\u2009weeks) and lack of lifestyle intervention were associated with greater improvements in insulin resistance and hormone levels. Lipid outcomes were consistent across subgroups, while glycaemic improvements were more notable in overweight versus obese women. Sensitivity analyses supported the robustness of findings. However, the overall certainty of evidence was low due to risk of bias and heterogeneity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combination of liraglutide and metformin resulted in greater improvements in body weight, blood sugar levels, insulin sensitivity, hormone balance (including LH, FSH and testosterone) and cholesterol profiles. These findings indicate that the combined therapy offers more comprehensive metabolic and hormonal benefits than metformin alone for women with PCOS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70028","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T08:17:13Z","timestamp":1756196233000},"page":"6139-6153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Combined liraglutide and metformin therapy in overweight or obese women with polycystic ovary syndrome: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"27","author":[{"given":"Jing","family":"Ling","sequence":"first","affiliation":[{"name":"Guangzhou University of Chinese Medicine  Guanzhou Guangdong China"},{"name":"Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine  Guanzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenrui","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine  Guanzhou Guangdong China"},{"name":"Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Zhen","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine  Guanzhou Guangdong China"},{"name":"Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine  Guanzhou Guangdong China"},{"name":"Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingzi","family":"Fang","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine  Guanzhou Guangdong China"},{"name":"Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencong","family":"Song","sequence":"additional","affiliation":[{"name":"Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1358-5477","authenticated-orcid":false,"given":"Xuelian","family":"Du","sequence":"additional","affiliation":[{"name":"Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad463"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2023.103821"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2018.11.002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.11.003"},{"issue":"6","key":"e_1_2_10_6_1","first-page":"3","article-title":"Research progress on pregnancy complications in polycystic ovary syndrome","volume":"19","author":"Zhang CL","year":"2018","journal-title":"Chin J Clin Obstet Gynecol"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2018.04.008"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0254\u20106450.2019.12.006"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063\u2010023\u201007569\u20106"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh098"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.endmts.2025.100228"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejendo\/lvad096"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD005552.pub3"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471\u20100528.14623"},{"issue":"16","key":"e_1_2_10_15_1","first-page":"2","article-title":"Current research on the clinical pharmacology of metformin in the treatment of diabetes","volume":"7","author":"Tang LT","year":"2019","journal-title":"Chin J Integr Tradit West Med Cardiovasc Dis Electron Ed"},{"issue":"11","key":"e_1_2_10_16_1","article-title":"Research progress on the role of gut microbiota in the hypoglycemic mechanism of metformin","volume":"39","author":"Feng J","year":"2019","journal-title":"Chin J Gerontol"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1156521"},{"issue":"35","key":"e_1_2_10_18_1","first-page":"2","article-title":"Clinical observation of liraglutide combined with metformin in the treatment of type 2 diabetes mellitus complicated with polycystic ovary syndrome","volume":"7","author":"Wang AY","year":"2020","journal-title":"Pract Gynecol Endocrinol Electron J"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.15887\/j.cnki.13\u20101389\/r.2020.29.029"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.70749\/ijbr.v3i3.818"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12902\u2010017\u20100155\u20109"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12905-025-03787-z"},{"key":"e_1_2_10_23_1","unstructured":"XiaohuiGUet al.The effectiveness of liraglutide combined with metformin in improving glycolipid metabolism and hormonal levels in polycystic ovary syndrome: a meta\u2010analysis.2025;46(3):79\u201088."},{"issue":"3","key":"e_1_2_10_24_1","first-page":"e123","article-title":"Preferred reporting items for systematic reviews and meta\u2010analyses: the PRISMA statement","volume":"3","author":"Moher D","year":"2009","journal-title":"Open Med Peer\u2010Rev Indep Open\u2010Access J"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE\u201013\u20100797"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.1674\u20105809.2015.07.009"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE\u201018\u20100175"},{"issue":"9","key":"e_1_2_10_28_1","first-page":"43","article-title":"Clinical observation on liraglutide combined with metformin in the treatment of type 2 diabetes mellitus complicated with polycystic ovary syndrome","volume":"57","author":"Zhao D","year":"2019","journal-title":"Chin Mod Doct"},{"issue":"32","key":"e_1_2_10_29_1","first-page":"36","article-title":"Clinical effect of liraglutide combined with metformin hydrochloride in treating PCOS with glucose and lipid metabolism disorder","volume":"26","author":"Zhang B","year":"2019","journal-title":"China Contemp Med"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.14053\/j.cnki.ppcr.202001012"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.16484\/j.cnki.issn2095\u20108803.2020.35.025"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.16484\/j.cnki.issn2095\u20108803.2020.03.012"},{"issue":"5","key":"e_1_2_10_33_1","first-page":"132","article-title":"Clinical effect of liraglutide in treating impaired glucose tolerance complicated by PCOS","volume":"16","author":"Zhou JL","year":"2020","journal-title":"Pract J Diabetes"},{"issue":"12","key":"e_1_2_10_34_1","first-page":"1634","article-title":"Effect of liraglutide treatment on fertility in obese women with PCOS","volume":"36","author":"Yang Q","year":"2021","journal-title":"J North Sichuan Med Coll"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.16658\/j.cnki.1672\u20104062.2021.01.014"},{"issue":"8","key":"e_1_2_10_36_1","first-page":"1654","article-title":"Effect of liraglutide combined with metformin on ovarian function in patients with PCOS","volume":"36","author":"Sun HY","year":"2021","journal-title":"Mod Med Clin"},{"issue":"31","key":"e_1_2_10_37_1","first-page":"45","article-title":"Clinical efficacy of liraglutide as adjunct therapy in PCOS","volume":"8","author":"Liang S","year":"2021","journal-title":"Pract Gynecol Endocrinol Electron J"},{"issue":"9","key":"e_1_2_10_38_1","first-page":"2442","article-title":"Effects of liraglutide combined with metformin on glucose and lipid metabolism and reproductive function in PCOS patients","volume":"43","author":"Zheng L","year":"2022","journal-title":"Jilin Yi Xue"},{"issue":"9","key":"e_1_2_10_39_1","first-page":"74","article-title":"Effects of liraglutide combined with metformin on glucose\u2010lipid metabolism and reproductive function in obese women with PCOS","volume":"14","author":"Tan MD","year":"2022","journal-title":"Chin J Fam Plann Gynecol Obstet"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.19381\/j.issn.1001\u20107585.2022.10.037"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.945609"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.14035\/j.cnki.hljyy.2022.05.008"},{"issue":"10","key":"e_1_2_10_43_1","first-page":"1329","article-title":"Effects of liraglutide combined with metformin on sex hormones, insulin resistance, and adipocytokines in obese women with polycystic ovary syndrome","volume":"38","author":"Feng YJ","year":"2023","journal-title":"J North Sichuan Med Coll"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/17455057241311759"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2014.00140"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.12259\/j.issn.2095\u2010610X.S20250219"},{"key":"e_1_2_10_47_1","volume-title":"Polycystic Ovary Syndrome: Key Facts","author":"World Health Organization","year":"2025"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618\u2010021\u201001666\u20106"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.16422"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884\u2010025\u201007480\u20109"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618\u2010023\u201002084\u20106"},{"key":"e_1_2_10_52_1","volume-title":"StatPearls [Internet]","author":"Cerillo JL","year":"2025"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12720"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2016.3081"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12041454"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1526109"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC\u201024\u20100529"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.55014\/pij.v8i2.794"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.120.315708"},{"issue":"2","key":"e_1_2_10_60_1","first-page":"187","article-title":"Metformin\u2010clinical pharmacology in PCOs","volume":"8","author":"Dumitrescu R","year":"2015","journal-title":"J Med Life"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.54393\/pjhs.v6i5.2980"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.70028","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/full-xml\/10.1111\/dom.70028","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.70028","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T06:23:57Z","timestamp":1771309437000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.70028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":60,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/dom.70028"],"URL":"https:\/\/doi.org\/10.1111\/dom.70028","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.70028\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70028\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70028\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70028\/v1\/review1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]},"assertion":[{"value":"2025-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}