Review of the Potential Effects of Semaglutide and Metformin in the Management of Polycystic Ovary Syndrome (PCOS) and Obesity
Abstract
Polycystic ovary syndrome (PCOS) is considered a lifestyle disorder. Various lifestyle factors hinder obesity and insulin resistance, which worsen the symptoms of PCOS and this makes existing treatment very challenging. This review examines 10 studies on the effectiveness of combining glucagon-like peptide-1 (GLP-1) receptor agonists, particularly liraglutide and semaglutide, with metformin for weight control in women with PCOS. Results declared that combined therapy gives greater effects in terms of weight loss and metabolic improvement. Combined liraglutide with metformin led to an average weight reduction of 6.5 ± 29.55 kg and side-by-side reductions in body mass index (BMI), fasting glucose and insulin levels over 12 weeks. While comparing the monotherapy of metformin and liraglutide, liraglutide was more effective for weight loss, but the combination is thought to be impactful. Semaglutide monotherapy also emerged as a strong alternative, achieving a 9 kg weight reduction within 12 weeks in obese PCOS patients and was well-tolerated with minimal side effects. These findings suggest that combining semaglutide with metformin may be an effective approach for weight and metabolic issues in PCOS women, with semaglutide offering additional promise. Further studies are encouraged to refine dosing and explore long-term benefits.
References
Bulsara J, Patel P, Soni A, Acharya S. A review: brief insight into polycystic ovarian syndrome. Endocr Metab Sci. 2021;3:100085; doi: 10.1016/j.endmts.2021.100085.
Vidya Bharathi R, Swetha S, Neerajaa J, Madhavica JV, Janani DM, Rekhaet SN, al. An epidemiological survey: Effect of predisposing factors for PCOS in Indian urban and rural population. Middle East Fertil Soc J. 2017;22(4):313–6. doi: 10.1016/j.mefs.2017.05.007.
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004 Jan;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004.
Hart R, Hickey M, Franks S. Definitions, prevalence and symptoms of polycystic ovaries and polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004;18(5):671–83. doi: 10.1016/j.bpobgyn.2004.05.001.
Pandey A, Pal AK, Chawla G, Ansari S, Mandal J. A Review on health care surveillance of PCOD. Prim Sci Med Public Health 2023. doi: 10.56831/PSMPH-03-102.
Shrestha A, Dixit A, Zaidi A. Assessment of lifestyle and diet modification of patients suffering from polycystic ovarian disease (PCOD) in North India. J Food Nutr Sci. 2019;7(4):60. doi: 10.11648/j.jfns.20190704.12.
Barbieri R. Metformin for the treatment of polycystic ovary syndrome. Obstet Gynecol. 2003;101(4):785–93. doi: 10.1016/S0029-7844(03)00045-0.
Zhang L, Feng Y, Sun X, Yi S, Xiao X, Ma F. Impact of body mass index on assisted reproductive technology outcomes in patients with polycystic ovary syndrome: a meta-analysis. Reprod Biomed Online. 2024 Jun;48(6):103849. doi: 10.1016/j.rbmo.2024.103849.
Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Consensus on women's health aspects of polycystic ovary syndrome (PCOS). Hum Reprod. 2012 Jan;27(1):14-24. doi: 10.1093/humrep/der396.
Sherif K, Coborn J, Hoovler A, Gill L. Medical journey of patients with polycystic ovary syndrome and obesity: a cross-sectional survey of patients and primary care physicians. Postgrad Med. 2023 Apr;135(3):312-20. doi: 10.1080/00325481.2022.2140511.
Lim SS, Davies MJ, Norman RJ, Moran LJ. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2012 Nov-Dec;18(6):618-37. doi: 10.1093/humupd/dms030.
Yildiz BO, Knochenhauer ES, Azziz R. Impact of obesity on the risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2008;93(1):162–8. doi: 10.1210/jc.2007-1834.
Teede HJ, Tay CT, Laven J, Dokras A, Moran LJ, Piltonen TT, et al; International PCOS Network. Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome†. Hum Reprod. 2023 Sep 5;38(9):1655-79. doi: 10.1093/humrep/dead156.
Bril F, Ezeh U, Amiri M, Hatoum S, Pace L, Chen YH, et al. Adipose tissue dysfunction in polycystic ovary syndrome. J Clin Endocrinol Metab. 2023 Dec 21;109(1):10-24. doi: 10.1210/clinem/dgad356.
Legro R. Obesity and PCOS: implications for diagnosis and treatment. Semin Reprod Med 2012;30(06):496–506. doi: 10.1055/s-0032-1328878.
Mathur R, Alexander CJ, Yano J, Trivax B, Azziz R. Use of metformin in polycystic ovary syndrome. Am J Obstet Gynecol. 2008 Dec;199(6):596-609. doi: 10.1016/j.ajog.2008.09.010.
Chiu HY, Tsai SC, Tsai FJ, Lo YH, Cheng CC, Liu TY, et al. Liraglutide with metformin therapy ameliorates hepatic steatosis and liver injury in a mouse model of non-alcoholic steatohepatitis. In Vivo. 2023 May-Jun;37(3):1037-1046. doi: 10.21873/invivo.13178.
Haas DA, Carr BR, Attia GR. Effects of metformin on body mass index, menstrual cyclicity, and ovulation induction in women with polycystic ovary syndrome. Fertil Steril. 2003;79(3):469–81. doi: 10.1016/S0015-0282(02)04800-8.
Harborne LR, Sattar N, Norman JE, Fleming R. Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses. J Clin Endocrinol Metab. 2005 Aug;90(8):4593-8. doi: 10.1210/jc.2004-2283.
Hughes S, Neumiller JJ. Oral semaglutide. Clin Diabetes. 2020 Jan;38(1):109-11. doi: 10.2337/cd19-0079.
Abu-Hamdah R, Rabiee A, Meneilly GS, Shannon RP, Andersen DK, Elahi D. Clinical review: The extrapancreatic effects of glucagon-like peptide-1 and related peptides. J Clin Endocrinol Metab. 2009 Jun;94(6):1843-52. doi: 10.1210/jc.2008-1296.
Jensterle Sever M, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2014 Feb 7;170(3):451-9. doi: 10.1530/EJE-13-0797.
Yanai H, Hakoshima M, Adachi H, Katsuyama H. A significant effect of oral semaglutide on cardiovascular risk factors in patients with type 2 diabetes. Cardiol Res. 2022 Oct;13(5):303-8. doi: 10.14740/cr1441.
Isaacs DM, Kruger DF, Spollett GR. Optimizing therapeutic outcomes with oral semaglutide: a patient-centered approach. Diabetes Spectr. 2021 Jan;34(1):7-19. doi: 10.2337/ds20-0016.
Kane MP, Triplitt CL, Solis-Herrera CD. Management of type 2 diabetes with oral semaglutide: Practical guidance for pharmacists. Am J Health Syst Pharm. 2021;78(7):556–67. doi: 10.1093/ajhp/zxaa413.
Carmina E, Longo RA. Semaglutide treatment of excessive body weight in obese PCOS patients unresponsive to lifestyle programs. J Clin Med. 2023;12(18):5921. doi: 10.3390/jcm12185921.
Ghusn W, De la Rosa A, Sacoto D, Cifuentes L, Campos A, Feris F, et al. Weight loss outcomes associated with semaglutide treatment for patients with overweight or obesity. JAMA Netw Open. 2022 Sep 1;5(9):e2231982. doi: 10.1001/jamanetworkopen.2022.31982.
Ard J, Fitch A, Fruh S, Herman L. Weight loss and maintenance related to the mechanism of action of glucagon-like peptide 1 receptor agonists. Adv Ther. 2021 Jun;38(6):2821-39. doi: 10.1007/s12325-021-01710-0.
Tamayo-Trujillo R, Ruiz-Pozo VA, Cadena-Ullauri S, Guevara-Ramírez P, Paz-Cruz E, Zambrano-Villacres R, et al. Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity. Front Nutr. 2024 Apr 29;11:1398059. doi: 10.3389/fnut.2024.1398059.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
