Therapeutic Potential of Glucagon-like Peptide-1 Agonists in Polycystic Ovary Syndrome: From Current Clinical Evidence to Future Perspectives

Abstract

Despite the continuous effort to understand the pathophysiology and determine potential therapeutic targets, PCOS treatment largely depends on lifestyle intervention and symptomatic management of individual signs and symptoms. International guidelines recognize the importance of weight reduction as a cornerstone for the achievement of better metabolic, reproductive, and cardiovascular outcomes in PCOS women who are overweight or obese. With its profound weight loss potential in patients with or without diabetes, the administration of GLP-1 receptor agonists has been investigated in overweight/obese women with PCOS in several single-center randomized control trials with considerable variation in the dosing regimen, follow-up duration, and outcome measurements over recent years. Most trials reported superior weight loss effects of GLP-1 receptor agonists compared to lifestyle changes or metformin, with additional metabolic, reproductive, and cardiovascular benefits in this population. However, their use is currently not widely accepted by the clinical community that treats this population. The major concern is how to balance the reproductive and metabolic treatment strategies since the use of GLP-1 receptor agonists requires effective contraception while on therapy and a washout period before pregnancy. Both approaches are not mutually exclusive, yet the best choice requires a careful assessment of the clinical context. Knowing a patient’s individual circumstances, precise clinical sub-phenotyping, and regular monitoring are crucial components for the safe and effective use of these new tools. In the present narrative review, we explore the current clinical evidence and provide the future perspectives and challenges for their implementation in PCOS management.

Anti‐obesity pharmacological agents for polycystic ovary syndrome: A systematic review and meta‐analysis to inform the 2023 international evidence‐based guideline

“…Previous narrative reviews supporting the use of GLP-1 RAs in PCOS focused on single-center RCT and observational studies. 49 Two meta-analyses of GLP-1 RAs versus metformin in PCOS included six and eight RCT studies, respectively, 50,51 which concluded GLP-1 RAs were beneficial with or without metformin for metabolic, reproductive, and anthropometric parameters. However, these analyses combined exenatide and liraglutide in varying protocols and dosing regimens.…”

“…The interest in using GLP‐1 RAs in women with PCOS has increased, due to general efficacy in weight reduction. Previous narrative reviews supporting the use of GLP‐1 RAs in PCOS focused on single‐center RCT and observational studies 49 . Two meta‐analyses of GLP‐1 RAs versus metformin in PCOS included six and eight RCT studies, respectively, 50,51 which concluded GLP‐1 RAs were beneficial with or without metformin for metabolic, reproductive, and anthropometric parameters.…”

Insulin Metabolism in Polycystic Ovary Syndrome: Secretion, Signaling, and Clearance

“…Consequently, the treatment, to a large degree, still depends on lifestyle intervention and symptomatic management of individual signs and symptoms. The new era of anti-obesity therapy offers a novel powerful pharmacologic tool to improve metabolic, reproductive, and other clinical outcomes in a subset of patients who are overweight or obese, primarily through weight reduction [ 2 ]. However, a better understanding of individual patient phenotypes and the dominant pathophysiological process is necessary to improve the management of all patients.…”

Liraglutide and polycystic ovary syndrome: is it only a matter of body weight?

“…These effects still deserve a greater insight, especially in the light of a possible therapeutic use in PCOS women independently of obesity. Contrariwise, other relevant aspects, such as the safety profile and tolerability of GLP-1RA or the beneficial effects on fertility in PCOS, have been more extensively treated, especially considering that possible direct or indirect reproductive effects of GLP-1 RA might require a concomitant effective contraception and a washout period before pregnancy [22,[24][25][26][27][28][29][30][31].…”