The Use of GLP-1 Receptor Agonists in the Treatment of Obesity in Women with PCOS
DOI:
https://doi.org/10.12775/QS.2024.20.53831Keywords
Polycystic Ovary Syndrome, Obesity, Glucagon-Like Peptide-1 Receptor AgonistsAbstract
Introduction and aim of study: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting young women. It is diagnosed in individuals who meet 2 of the following 3 criteria: hyperandrogenism, ovarian dysfunction or polycystic ovarian morphology on ultrasound. A common component of this disease is obesity that leads to many serious health complications. This review paper aims to discuss the use of glucagon-like peptide-1 (GLP-1) receptor agonists as a therapeutic option to treat obesity in female patients with PCOS.
Materials and Methods: The authors conducted a comprehensive review of the literature available in databases: PubMed and Medline focusing on the terms “PCOS”, “GLP-1”, “obesity”.
Results: The first-line treatment of metabolic disorders in the course of PCOS is lifestyle modification. In patients who do not achieve sufficient results pharmacotherapy is recommended. Therapy with GLP-1 receptor agonists shows beneficial effects not only on weight loss, but also on metabolic and endocrine disorders. Studies have proven the superiority of these medications over metformin in the treatment of obesity associated with PCOS. However, the simultaneous use of GLP-1 receptor agonists and metformin may be beneficial for the patients.
Conclusions: GLP-1 receptor agonists appear to be a promising therapeutic option in obese women with PCOS according to safety profile and effectiveness proven in studies.
References
Yildiz BO, Bozdag G, Yapici Z, Esinler I, Yarali H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod. 2012 Oct;27(10):3067-73. DOI: 10.1093/humrep/des232
Rotterdam, E.A.-S.P.C.W.G. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan;19(1):41-7. DOI: 10.1093/humrep/deh098.
Bręborowicz GH, Rechberger T. Ginekologia tom 1 i 2, PZWL 2023
Franks S. Assessment and management of anovulatory infertility in polycystic ovary syndrome, Endocrinology and Metabolism Clinics of North America. Endocrinol Metab Clin North Am. 2003 Sep;32(3):639-51. DOI: 10.1016/s0889-8529(03)00044-6
Gilbert EW, Tay CT, Hiam DS, Teede H, Moran LJ. Comorbidities and complications of polycystic ovary syndrome: an overview of systematic reviews. Clin Endocrinol (Oxf). 2018 Dec;89(6):683-699. DOI: 10.1111/cen.13828
Sanchez-Garrido MA, Tena-Sempere M. Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies. Mol Metab. 2020; 35: 100937, DOI: 10.1016/j. molmet.2020.01.001
Drucker DJ. GLP-1 physiology informs the pharmacotherapy of obesity. Mol Metab. 2022 Mar:57:101351. DOI: 10.1016/j.molmet.2021.101351
Sanchez-Garrido MA, Tena-Sempere M. Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies. Mol Metab. 2020 May:35:100937. DOI: 10.1016/j.molmet.2020.01.001
Crespo RP, Bachega T, Mendonca BB, Gomes LG. An update of genetic basis of PCOS pathogenesis Arch Endocrinol Metab. 2018 Jun;62(3):352-361. DOI: 10.20945/2359-3997000000049
Hiam D, Moreno-Asso A, Teede HJ, Laven JSE, Stepto NK, Moran LJ. The genetics of polycystic ovary syndrome: an overview of candidate gene systematic reviews and genome-wide association studies. J Clin Med. 2019 Oct 3;8(10):1606. DOI: 10.3390/jcm8101606.
Rojas J, Chavez M, Olivar L, Rojas M, Morillo J, Mejias J. Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth. Int J Reprod Med. 2014:2014:719050. DOI: 10.1155/2014/719050
Sadeghi HM, Adeli I, Calina D, et al. Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing. Int J Mol Sci. 2022; 23(2), DOI: 10.3390/ijms23020583.
Sirmans SM, Pate KA Epidemiology, diagnosis, and management of polycystic ovary syndrome Clin Epidemiol. 2013 Dec 18:6:1-13. DOI: 10.2147/CLEP.S37559
Franks S. The ubiquitous polycystic ovary. J Endocrinol. 1991 Jun;129(3):317-9. DOI: 10.1677/joe.0.1290317
Li Y, Chen C, Ma Y.. Multi-system reproductive metabolic disorder: significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS). Life Sci. 2019; 228: 167–175, DOI: 10.1016/j.lfs.2019.04.046.
Dewailly D, Barbotin AL, Dumont A, et al. Role of Anti-Müllerian Hormone in the Pathogenesis of Polycystic Ovary Syndrome. Front Endocrinol (Lausanne). 2020; 11: 641, DOI: 10.3389/fendo.2020.00641.
Zeng X, Xie YJ, Liu YT. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2020; 502: 214–221, DOI: 10.1016/j.cca.2019.11.003.
Greenwood EA, Huddleston HG. Insulin resistance in polycystic ovary syndrome: concept versus cutoff. Fertil Steril. 2019; 112(5): 827–828, DOI: 10.1016/j.fertnstert.2019.08.100.
Dunaif A. Drug insight: insulin-sensitizing drugs in the treatment of polycystic ovary syndrome--a reappraisal. Nat Clin Pract Endocrinol Metab. 2008 May;4(5):272-83. DOI: 10.1038/ncpendmet0787
Baranowska-Bik A. Therapy of obesity in women with PCOS using GLP-1 analogues - benefits and limitations. Endokrynol Pol 2022;73(3):627-643 DOI: 10.5603/EP.a2022.0047
Barber TM, Franks S. Obesity and polycystic ovary syndrome. ClinEndocrinol (Oxf). 2021; 95(4): 531–541, DOI: 10.1111/cen.14421.
Allen LA, Shrikrishnapalasuriyar N, Rees DA. Long-term health outcomes in young women with polycystic ovary syndrome: A narrative review. Clin Endocrinol (Oxf). 2021, DOI: 10.1111/cen.14609.
Cena H, Chiovato L, Nappi RE. Obesity, Polycystic Ovary Syndrome, and Infertility: A New Avenue for GLP-1 Receptor Agonists. J Clin Endocrinol Metab. 2020; 105(8), DOI: 10.1210/clinem/dgaa285.
Kim CH, Lee SH. Effectiveness of Lifestyle Modification in Polycystic OvarySyndrome Patients with Obesity: A Systematic Review and nMeta-Analysis. Life (Basel). 2022; 12(2), DOI: 10.3390/life12020308.
Moghetti P, Tosi F, Bonin C, Di Sarra D, Fiers T, Kaufman J.M, Giagulli V.A, Signoriello G, Simoni M. Divergences in insulin resistance between the different phenotypes of the polycystic ovary syndrome. J Clin Endocrinol Metab. 2013 Apr;98(4):E628-37. DOI: 10.1210/jc.2012-3908
Rashid R, Mir SA, Kareem O, et al. Polycystic ovarian syndrome-current pharmacotherapy and clinical implications. Taiwan J Obstet Gynecol. 2022; 61(1): 40–50, DOI: 10.1016/j.tjog.2021.11.009.
Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism. 1994 May;43(5):647-54. DOI: 10.1016/0026-0495(94)90209-7
Yaribeygi H, Sathyapalan T, Sahebkar A. Molecular mechanisms by which GLP-1 RA and DPP-4i induce insulin sensitivity. Life Sci. 2019; 234: 116776, DOI: 10.1016/j.lfs.2019.116776.
Abdalla MA, Deshmukh H, Atkin S, et al. A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2020; 11: 2042018820938305, DOI: 10.1177/2042018820938305.
Campbell J., Beaudry J., Svendsen B., Baggio L., Gordon A., Ussher J., Wong CK., Gribble F., D’Alessio D., Reimann F., Drucker D., GIPR Is Predominantly Localized to Nonadipocyte Cell Types Within White Adipose Tissue. Diabetes. 2022 May 1;71(5):1115-1127. DOI: 10.2337/db21-1166.
Thorens B. Expression cloning of the pancreatic beta cell receptor for the gluco-incretin hormone glucagon-like peptide 1. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8641-5. DOI: 10.1073/pnas.89.18.8641
McLean B., Won CK., Campbell J., Hodson D., Trapp S., Drucker D., “Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation” Endocr Rev. 2021 Mar 15;42(2):101-132. DOI: 10.1210/endrev/bnaa032
Müller TD, Finan B, Bloom SR, D’Alessio D, Drucker DJ, Flatt PR, Fritsche A, Gribble F, Grill HJ, Habaner JF. Glucagon-like peptide 1 (GLP-1) Mol. Metab. 2019;30:72–130. DOI: 10.1016/j.molmet.2019.09.010.
Sinha R., Papamargaritis D., Sargeant J., Davies M., ”Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management” J Obes Metab Syndr. 2023 Mar 30;32(1):25-45. DOI: 10.7570/jomes22067. Epub 2023 Feb 8.
Moran LJ. Hutchison SK. Norman RJ Teede HJ..Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2011 Feb 16:(2):CD007506. DOI: 10.1002/14651858
Rasmussen CB, Lindenberg S. The effect of liraglutide on weight loss in women with polycystic ovary syndrome: an observational study. Front Endocrinol (Lausanne). 2014 Aug 27:5:140. DOI: 10.3389/fendo.2014.00140
Szczesnowicz A, Szeliga A, Niwczyk O, Bala G, Meczekalski B. Do GLP-1 Analogs Have a Place in the Treatment of PCOS? New Insights and Promising Therapies. J Clin Med. 2023;12(18):5915. DOI:10.3390/JCM12185915
Ge JJ, Wang DJ, Song W, Shen SM, Ge WH. The effectiveness and safety of liraglutide in treating overweight/obese patients with polycystic ovary syndrome: a meta-analysis. J Endocrinol Invest. 2022 Feb;45(2):261-273. DOI: 10.1007/s40618-021-01666-6
Jensterle M, Kravos NA, Pfeifer M, Kocjan T, Janez A. A 12-week treatment with the long-acting glucagon-like peptide 1 receptor agonist liraglutide leads to significant weight loss in a subset of obese women with newly diagnosed polycystic ovary syndrome. Hormones (Athens). 2015 Jan-Mar;14(1):81-90. DOI: 10.1007/BF03401383
Srinivasan D, Lofton HF. Effect of GLP-1 agonists on weight loss in patients with polycystic ovary syndrome and obesity: A single-center study. Obes Pillars. 2022 Apr 10:2:100016. DOI: 10.1016/j.obpill.2022.100016
Kahal H, Kilpatrick Es, Rigby As, Coady Am, Atkin Sl. The effects of treatment with liraglutide on quality of life and depression in young obese women with PCOS and controls. Gynecol Endocrinol. 2019 Feb;35(2):142-145. DOI: 10.1080/09513590.2018.1505848.
Meloni AR, Deyoung MB, Lowe C, Parkes DG. GLP-1 Receptor Activated Insulin Secretion from Pancreatic β-Cells: Mechanism and Glucose Dependence. Diabetes Obes. Metab. 2013;15:15–27. DOI: 10.1111/j.1463-1326.2012.01663.
Müller TD, Finan B, Bloom SR, D’Alessio D, Drucker DJ, Flatt PR, Fritsche A, Gribble F, Grill HJ, Habener JF. Glucagon-like Peptide 1 (GLP-1) Mol. Metab. 2019;30:72–130. DOI: 10.1016/j.molmet.2019.09.010.
Pfeiffer AFH, Keyhani-Nejad F. High Glycemic Index Metabolic Damage—A Pivotal Role of GIP and GLP-1. Trends Endocrinol. Metab. 2018;29:289–299. DOI: 10.1016/j.tem.2018.03.003.
Bednarz K, Kowalczyk K, Cwynar M, Czapla D, Czarkowski W, Kmita D, Nowak A, Madej P. The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome. Int J Mol Sci. 2022 Apr 14;23(8):4334. DOI: 10.3390/ijms23084334
Elkind-Hirsch KE, Chappell N, Shaler D, Storment J, Bellanger D. Liraglutide 3 mg on weight, body composition, and hormonal and metabolic parameters in women with obesity and polycystic ovary syndrome: a randomized placebo-controlled-phase 3 study. Fertil Steril. 2022 Aug;118(2):371-381. DOI: 10.1016/j.fertnstert.2022.04.027
Michałowska J, Miller-Kasprzak E, Bogdański P. Incretin hormones in obesity and related cardiometabolic disorders: the clinical perspective. Nutrients. 2021 Jan 25;13(2):351. DOI: 10.3390/nu13020351
Palomba S. Is fertility reduced in ovulatory women with polycystic ovarysyndrome? An opinion paper. Hum Reprod. 2021; 36(9): 2421–2428, DOI: 10.1093/humrep/deab181.
Jensterle M, Janez A, Fliers E, DeVries JH, Vrtacnik-Bokal E, Siegelaar SE. The role of glucagon-like peptide-1 in reproduction: from physiology to therapeutic perspective. Hum Reprod Update. 2019 Jul 1;25(4):504-517. DOI: 10.1093/humupd/dmz019
Han Y, Li Y, He B. GLP-1 receptor agonists versus metformin in PCOS: a systematic review and meta-analysis. Reprod Biomed Online. 2019;39(2):332-342. DOI:10.1016/j.rbmo.2019.04.017
Lamoia TE, Shulman GI. Cellular and Molecular Mechanisms of Metformin Action. Endocr Rev. 2021;42(1):77-96. DOI:10.1210/ENDREV/BNAA023
Dutta S, Shah RB, Singhal S, et al. Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes. Drug Des Devel Ther. 2023;17:1907-1932. DOI:10.2147/DDDT.S409373
Zhao H, Xing C, Zhang J, He B. Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis. Reprod Health. 2021;18(1). DOI:10.1186/S12978-021-01207-7
Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes e state-of-the-art. Mol Metab. 2021;46:101102. DOI:10.1016/j.molmet.2020.101102
Saxena AR, Frias JP, Brown LS, et al. Efficacy and Safety of Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist Danuglipron for Glycemic Control Among Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA Netw Open. 2023;6(5):e2314493. DOI:10.1001/JAMANETWORKOPEN.2023.14493
Elkind-Hirsch K, Marrioneaux O, Bhushan M, Vernor D, Bhushan R. Comparison of Single and Combined Treatment with Exenatide and Metformin on Menstrual Cyclicity in Overweight Women with Polycystic Ovary Syndrome. 2670 jcem.endojournals.org J Clin Endocrinol Metab. 2008;93(7):2670-2678. DOI:10.1210/jc.2008-0115
Kahal H, Abouda G, Rigby AS, Coady AM, Kilpatrick ES, Atkin SL. Glucagon-like peptide-1 analogue, liraglutide, improves liver fibrosis markers in obese women with polycystic ovary syndrome and nonalcoholic fatty liver disease. Clin Endocrinol (Oxf). 2014;81(4):523-528. DOI:10.1111/CEN.12369
Arefhosseini S, Ebrahimi-Mameghani M, Najafipour F, Tutunchi H. Non-alcoholic fatty liver disease across endocrinopathies: Interaction with sex hormones. Published online 2022. DOI:10.3389/fendo.2022.1032361
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