{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:07:19Z","timestamp":1793390839320,"version":"4.5.0"},"reference-count":33,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.ejphar.2025.178055","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T05:25:39Z","timestamp":1755235539000},"page":"178055","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["The effects of metformin and sitagliptin for polycystic ovary syndrome treatment are enhanced by combining them"],"prefix":"10.1016","volume":"1005","author":[{"given":"Zeinab Ranjbar","family":"Kaboutarkhani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahereh","family":"Foroutan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Eini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2025.178055_bib1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s00404-020-05951-2","article-title":"Association of metabolic and inflammatory markers with polycystic ovarian syndrome (PCOS): an update","volume":"303","author":"Abraham Gnanadass","year":"2021","journal-title":"Arch. Gynecol. Obstet."},{"key":"10.1016\/j.ejphar.2025.178055_bib2","article-title":"Alteration of IL-6, BMP-15 and GDF-9 levels on PCOS rat models after treated with Syzygium Polyanthum (Wight) Walp leaves extract","volume":"15","author":"Aditya","year":"2023","journal-title":"Pharmacogn. J."},{"key":"10.1016\/j.ejphar.2025.178055_bib3","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0015-0282(01)01975-6","article-title":"Metformin directly inhibits androgen production in human thecal cells","volume":"76","author":"Attia","year":"2001","journal-title":"Fertil. Steril."},{"key":"10.1016\/j.ejphar.2025.178055_bib4","article-title":"Role of metformin in polycystic ovary syndrome (PCOS)-related infertility","volume":"15","author":"Attia","year":"2023","journal-title":"Cureus"},{"issue":"6","key":"10.1016\/j.ejphar.2025.178055_bib6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11892-024-01539-1","article-title":"Metformin: past, present, and future","volume":"24","author":"Chaudhary","year":"2024","journal-title":"Curr. Diabetes Rep."},{"key":"10.1016\/j.ejphar.2025.178055_bib8","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.3390\/diagnostics13061113","article-title":"Current guidelines for diagnosing PCOS","volume":"13","author":"Christ","year":"2023","journal-title":"Diagnostics"},{"key":"10.1016\/j.ejphar.2025.178055_bib9","doi-asserted-by":"crossref","DOI":"10.1111\/jfbc.14462","article-title":"Nasturtium officinale L. and metformin alleviate the estradiol\u2010induced polycystic ovary syndrome with synergistic effects through modulation of Bax\/Bcl\u20102\/p53\/caspase\u20103 signaling pathway and anti\u2010inflammatory and anti\u2010oxidative effects","volume":"46","author":"Cui","year":"2022","journal-title":"J. Food Biochem."},{"issue":"12","key":"10.1016\/j.ejphar.2025.178055_bib10","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.tem.2020.09.002","article-title":"Sitagliptin\/metformin: a new medical treatment in polycystic ovary syndrome","volume":"31","author":"Daneshjou","year":"2020","journal-title":"Trends Endocrinol. Metabol."},{"key":"10.1016\/j.ejphar.2025.178055_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.jri.2022.103499","article-title":"Sitagliptin\/metformin improves the fertilization rate and embryo quality in polycystic ovary syndrome patients through increasing the expression of GDF9 and BMP15: a new alternative to metformin (a randomized trial)","volume":"150","author":"Daneshjou","year":"2022","journal-title":"J. Reprod. Immunol."},{"key":"10.1016\/j.ejphar.2025.178055_bib12","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1210\/en.2014-1765","article-title":"Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model","volume":"156","author":"Di Pietro","year":"2015","journal-title":"Endocrinology"},{"key":"10.1016\/j.ejphar.2025.178055_bib16","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.mefs.2010.10.003","article-title":"The role of metformin in ovulation induction: current status","volume":"16","author":"Elnashar","year":"2011","journal-title":"Middle East Fertil. Soc. J."},{"key":"10.1016\/j.ejphar.2025.178055_bib17","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1089\/met.2017.0095","article-title":"Dipeptidyl peptidase-4 inhibitor sitagliptin prevented weight regain in obese women with polycystic ovary syndrome previously treated with liraglutide: a pilot randomized study","volume":"15","author":"Ferjan","year":"2017","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"10.1016\/j.ejphar.2025.178055_bib18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4158\/EP-2017-0027","article-title":"DPP-4 inhibitor sitagliptin as a potential treatment option in metformin-intolerant obese women with polycystic ovary syndrome: a pilot randomized study","volume":"24","author":"Ferjan","year":"2018","journal-title":"Endocr. Pract."},{"key":"10.1016\/j.ejphar.2025.178055_bib19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13048-018-0427-7","article-title":"Effect of resveratrol and metformin on ovarian reserve and ultrastructure in PCOS: an experimental study","volume":"11","author":"Furat Rencber","year":"2018","journal-title":"J. Ovarian Res."},{"key":"10.1016\/j.ejphar.2025.178055_bib21","doi-asserted-by":"crossref","first-page":"743","DOI":"10.2147\/VHRM.S3105","article-title":"New combination treatments in the management of diabetes: focus on sitagliptin\u2013metformin","volume":"4","author":"Green","year":"2008","journal-title":"Vasc. Health Risk Manag."},{"key":"10.1016\/j.ejphar.2025.178055_bib22","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/5150684","article-title":"The effect of metformin on polycystic ovary syndrome in overweight women: a systematic review and meta\u2010analysis of randomized controlled trials","volume":"2020","author":"Guan","year":"2020","journal-title":"Int. J. Endocrinol."},{"key":"10.1016\/j.ejphar.2025.178055_bib30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13048-015-0203-x","article-title":"Does metformin improve in vitro maturation and ultrastructure of oocytes retrieved from estradiol valerate polycystic ovary syndrome-induced rats","volume":"8","author":"Mesbah","year":"2015","journal-title":"J. Ovarian Res."},{"key":"10.1016\/j.ejphar.2025.178055_bib31","doi-asserted-by":"crossref","first-page":"66","DOI":"10.4103\/ijmr.IJMR_2139_20","article-title":"Comparative evaluation of metformin & sitaformin in classic PCOS patients undergoing intracytoplasmic sperm injection: a randomized controlled pilot study","volume":"157","author":"Modarres","year":"2023","journal-title":"Indian J. Med. Res."},{"key":"10.1016\/j.ejphar.2025.178055_bib32","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.lfs.2017.10.020","article-title":"Hormone-induced rat model of polycystic ovary syndrome: a systematic review","volume":"191","author":"Noroozzadeh","year":"2017","journal-title":"Life Sci."},{"key":"10.1016\/j.ejphar.2025.178055_bib33","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/rmb2.12262","article-title":"Animal models of polycystic ovary syndrome: a review of hormone\u2010induced rodent models focused on hypothalamus\u2010pituitary\u2010ovary axis and neuropeptides","volume":"18","author":"Osuka","year":"2019","journal-title":"Reprod. Med. Biol."},{"key":"10.1016\/j.ejphar.2025.178055_bib34","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.fertnstert.2017.06.026","article-title":"Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline","volume":"108","author":"Penzias","year":"2017","journal-title":"Fertil. Steril."},{"key":"10.1016\/j.ejphar.2025.178055_bib35","first-page":"87","article-title":"Effects of blastocyst artificial collapse prior to vitrification on hatching and survival rates and the expression of klf4 gene in mouse embryos","author":"Pooyanfar","year":"2018","journal-title":"Vet. Res. Forum"},{"key":"10.1016\/j.ejphar.2025.178055_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.repbio.2023.100763","article-title":"The effect of sitagliptin combined with rosiglitazone on autophagy and inflammation in polycystic ovary syndrome by regulating PI3K\/AKT\/mTOR and TLR4\/NF-\u03baB pathway","volume":"23","author":"Ren","year":"2023","journal-title":"Reprod. Biol."},{"key":"10.1016\/j.ejphar.2025.178055_bib40","first-page":"1","article-title":"Sitagliptin suppresses apoptotic cell death and histological changes in the ovaries of rats with polycystic ovary syndrome","volume":"7","author":"Safaeian","year":"2021","journal-title":"Archiv. Med. Lab. Sci."},{"key":"10.1016\/j.ejphar.2025.178055_bib42","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1007\/s10815-022-02625-7","article-title":"A brief insight into the etiology, genetics, and immunology of polycystic ovarian syndrome (PCOS)","volume":"39","author":"Siddiqui","year":"2022","journal-title":"J. Assist. Reprod. Genet."},{"key":"10.1016\/j.ejphar.2025.178055_bib43","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0002-9378(15)30642-6","article-title":"Amenorrhea associated with bilateral polycystic ovaries","volume":"29","author":"Stein","year":"1935","journal-title":"Am. J. Obstet. Gynecol."},{"key":"10.1016\/j.ejphar.2025.178055_bib45","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1177\/1933719116635278","article-title":"Effects of exenatide on metabolic changes, sexual hormones, inflammatory cytokines, adipokines, and weight change in a DHEA-treated rat model","volume":"23","author":"Sun","year":"2016","journal-title":"Reprod. Sci."},{"key":"10.1016\/j.ejphar.2025.178055_bib46","first-page":"4013","article-title":"Phosphodiesterase 4 inhibitor plus metformin is superior to metformin alone for the treatment of polycystic ovary syndrome: a rat model study","volume":"17","author":"Tohma","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.ejphar.2025.178055_bib49","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1080\/15384101.2019.1652036","article-title":"Metformin and sitagliptin combination therapy ameliorates polycystic ovary syndrome with insulin resistance through upregulation of lncRNA H19","volume":"18","author":"Wang","year":"2019","journal-title":"Cell Cycle"},{"key":"10.1016\/j.ejphar.2025.178055_bib50","doi-asserted-by":"crossref","DOI":"10.1155\/jfbc\/1184854","article-title":"Pharmacological appraisal of aqueous ethanolic extract of Cuminum cyminum (Cumin Seeds) in obesity and endocrinopathies associated with polycystic ovarian syndrome in animal models","author":"Wang","year":"2024","journal-title":"J. Food Biochem."},{"key":"10.1016\/j.ejphar.2025.178055_bib51","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1507\/endocrj.EJ21-0480","article-title":"Metformin ameliorates polycystic ovary syndrome in a rat model by decreasing excessive autophagy in ovarian granulosa cells via the PI3K\/AKT\/mTOR pathway","volume":"69","author":"Xu","year":"2022","journal-title":"Endocr. J."},{"key":"10.1016\/j.ejphar.2025.178055_bib54","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s13679-019-00335-3","article-title":"Metformin: mechanisms in human obesity and weight loss","volume":"8","author":"Yerevanian","year":"2019","journal-title":"Curr. Obes. Rep."},{"key":"10.1016\/j.ejphar.2025.178055_bib55","article-title":"Phytochemicals-based investigation of Rubia cordifolia pharmacological potential against letrozole-induced polycystic ovarian syndrome in female adult rats: in vitro, in vivo and mechanistic approach","volume":"10","author":"Zhang","year":"2024","journal-title":"Heliyon"}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S001429992500809X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S001429992500809X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:30:08Z","timestamp":1762144208000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S001429992500809X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":33,"alternative-id":["S001429992500809X"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178055","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The effects of metformin and sitagliptin for polycystic ovary syndrome treatment are enhanced by combining them","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178055","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"178055"}}