According to the 2023 international evidence-based guideline for polycystic ovary syndrome (PCOS), anti-obesity medications, including the glucagon-like peptide-1 (GLP-1) receptor agonists liraglutide and semaglutide, could be considered in addition to active lifestyle intervention for management of higher weight in adults with PCOS, consistent with general population obesity guidelines. Effective contraception is recommended when pregnancy is possible, as pregnancy safety data are lacking, and gradual dose escalation is advised to reduce gastrointestinal adverse effects. Shared decision-making should include discussion of potential side effects, the possible need for long-term therapy for weight management, the risk of weight regain after discontinuation, and the lack of long-term safety data. Anti-obesity agents are recommended for reproductive outcomes only in research settings until efficacy and safety are established. These recommendations were informed by a meta-analysis of 11 trials evaluating anti-obesity agents in PCOS, in which liraglutide, semaglutide, and orlistat appeared superior to placebo for anthropometric outcomes; however, evidence for hormonal, reproductive, metabolic, and psychological outcomes was limited, highlighting the need for further research. [1], [2]
A recent meta-analysis included 11 randomized controlled trials (RCTs) evaluating GLP-1 receptor agonists in women with PCOS. Compared with control, GLP-1 receptor agonists as add-on therapy were associated with a reduction in body mass index (mean difference [MD] −1.38 kg/m²; 95% confidence interval [CI] −2.39 to −0.38; low-certainty evidence). No differences were observed for low-density lipoprotein cholesterol or triglycerides, and evidence was insufficient to draw conclusions regarding glucose, insulin, hirsutism, or menstrual regularity. No studies evaluated quality of life, mental health, or cost-effectiveness. The authors concluded that GLP-1 receptor agonists are associated with modest short-term weight loss in women with PCOS and overweight or obesity; however, evidence for metabolic, reproductive, and psychological outcomes remains uncertain due to low-quality data. [3]
A 2024 meta-analysis of four RCTs involving 176 participants evaluated the efficacy and safety of GLP-1 receptor agonists (GLP-1 RAs) in women with PCOS and obesity. Compared to placebo, GLP-1 RA treatment resulted in a significant reduction in waist circumference (MD -5.16 cm; 95% CI -6.11 to -4.21; p<0.00001) and body mass index (BMI; MD -2.42; 95% CI -3.10 to -1.74; p<0.00001). Treatment also significantly lowered serum triglycerides (MD -0.20 mmol/L) and total testosterone levels (MD -1.33 nmol/L). However, no significant differences were found for total cholesterol (MD -0.04 mmol/L) or HOMA-IR (MD -0.30). Adverse events, primarily mild gastrointestinal symptoms, were more common with GLP-1 RAs (49 out of 112 patients) compared to placebo (9 out of 60), but led to only two treatment discontinuations. The results suggest that GLP-1 RAs are an effective intervention for reducing weight, improving lipid profiles, and lowering androgen levels in this patient population. [4]
Another 2021 review discusses the clinical potential of exenatide and liraglutide, particularly for overweight or obese PCOS women, and those with glucose intolerance or seeking fertility treatment. The trials detailed in the publication demonstrate significant improvements associated with GLP-1 RAs, including reductions in body weight, insulin resistance, and cardiovascular disease markers. Some of these studies also showed enhancements in reproductive health outcomes, such as improved menstrual regularity and higher pregnancy rates. The combination therapy of GLP-1 RAs with metformin seemed especially promising, showing superior efficacy compared to the agents used individually in managing symptoms like hyperandrogenism and metabolic dysfunctions. Furthermore, GLP-1 RAs were noted for their safety, with the most common adverse effects being manageable gastrointestinal symptoms. The review suggests that these agonists are a viable therapeutic option for PCOS, offering a multifaceted approach to addressing the syndrome's diverse manifestations. [5]
A 2023 comprehensive analysis utilized various clinical trials to explore the potential benefits of GLP-1RAs in addressing the complex metabolic challenges associated with PCOS. The therapeutic potential of GLP-1RAs was examined in overweight women with PCOS, focusing on weight reduction, improvement of hyperlipidemia, and enhancement of insulin sensitivity. The findings demonstrated notable weight loss and significant reduction in glycated hemoglobin levels among participants treated with GLP-1RAs, indicating a positive impact on glucose metabolism. GLP-1RAs exert their effects via a dual mechanism by promoting satiety and reducing appetite, while also enhancing insulin secretion in a glucose-dependent manner. Moreover, the anti-inflammatory effects of these agents contributed to the overall improvement in metabolic parameters. However, long-term safety concerns, particularly relating to pancreatic and thyroid effects, prompted the recommendation for careful patient screening and monitoring throughout the treatment duration. [6]
A 2019 meta-analysis evaluated the therapeutic efficacy of GLP-1 receptor agonists in comparison to metformin for treating PCOS. The meta-analysis included eight RCTs involving a total of 462 participants. The results demonstrated that compared to metformin, GLP-1 receptor agonists significantly improved insulin sensitivity (standardized mean difference [SMD] −0.40; 95% CI −0.74 to −0.06) and resulted in greater reductions in BMI (SMD −1.02; 95% CI −1.85 to −0.19) and abdominal girth (SMD −0.45; 95% CI −0.89 to −0.00). Further analysis indicated that while GLP-1 receptor agonists were more effective in certain metabolic outcomes, there was no significant difference between the two treatments concerning menstrual frequency, serum total testosterone levels, and the free androgen index. The assessment also highlighted a higher incidence of nausea and headaches with GLP-1 receptor agonists compared to metformin. Despite these findings, the overall quality of evidence was deemed moderate to low, suggesting that the conclusions should be interpreted with caution and highlighting the need for more high-quality research to confirm the benefits of GLP-1 receptor agonists in managing PCOS. [7]
A 2025 meta-analysis systematically assessed the efficacy and safety of GLP-1RAs compared to metformin and placebo in managing body weight, glucose homeostasis, and hormone levels in women with PCOS. The analysis included data from 13 randomized controlled trials with a total of 397 participants receiving GLP-1RAs, 330 receiving metformin, and 68 receiving placebo. The results found that GLP-1RAs significantly reduced BMI, body weight, waist circumference, waist-to-hip ratio, and abdominal girth, with a P-value of less than 0.0001 in all cases. Improvements in glucose homeostasis were evident as GLP-1RAs led to significant reductions in fasting insulin levels, glucose levels at 2 hours post-oral glucose tolerance test, and HOMA-IR. However, no significant changes were observed in fasting glucose levels when compared to metformin. While GLP-1RAs improved certain hormone levels when compared to placebo, these effects were not more pronounced than those achieved with metformin. In terms of safety, GLP-1RAs were associated with an increased incidence of nausea, vomiting, and dizziness, signaling the need for cautious consideration in clinical practice. Overall, the findings suggest GLP-1RAs as a promising alternative or adjunct to metformin, especially for those prioritizing weight loss and managing insulin resistance in PCOS. [8]
A 2025 meta-analysis compared the efficacy and safety of GLP1RAs combined with metformin versus metformin alone in managing PCOS. The analysis encompassed eight randomized controlled trials, incorporating a total of 337 participants. This meta-analysis systematically evaluated the impact of the combination therapy on various metabolic and hormonal outcomes, including body weight, BMI, waist circumference, fasting glucose, insulin sensitivity (HOMA-IR), androgen levels, and sex hormone-binding globulin (SHBG). The results from this meta-analysis indicated that the combination of GLP1RAs and metformin provides superior benefits compared to metformin alone, particularly in reducing body weight (MD -1.37 kg), BMI (MD -0.88 kg/m²), and waist circumference (MD -2.46 cm), with improvements in fasting glucose levels and insulin sensitivity as well. The hormonal outcomes demonstrated an increase in SHBG (MD 10.04), although changes in testosterone levels were not found to be statistically significant. Adverse events were similar between the groups, reaffirming the safety of the combination therapy. Collectively, this meta-analysis supports the potential of GLP1RAs combined with metformin to more effectively address the metabolic and hormonal challenges associated with PCOS compared to metformin alone. [9]
A 2024 systematic review and meta-analysis evaluated the efficacy and safety of GLP-1RAs in the treatment of PCOS among obese women. The analysis synthesized data from eight RCTs, encompassing a total of 519 participants, and comparing GLP-1RAs with other treatments such as metformin and dapagliflozin. Results demonstrated that GLP-1RAs significantly improved insulin sensitivity and contributed to reductions in BMI and waist circumference compared to control treatments. However, no significant differences were observed between GLP-1RAs and controls in terms of serum total testosterone, menstrual frequency, and free androgen index. The meta-analysis also reported a slight improvement in HDL cholesterol levels associated with GLP-1RA use. Although adverse events such as diarrhea were more common in the GLP-1RA group, incidences of nausea and vomiting did not significantly differ. The findings suggest that GLP-1RAs could be a promising therapeutic option for obese women with PCOS, particularly those with insulin resistance, though further high-quality, long-term studies are warranted. [10]
A 2025 review article analyzed the dual impact of GLP-1RAs on metabolic and reproductive health in women with PCOS. The review highlighted various studies demonstrating GLP-1RAs' efficacy in reducing fasting plasma glucose and hemoglobin A1c levels, improving glucose tolerance, and promoting significant weight loss, which in turn alleviates both metabolic and cardiovascular risks associated with PCOS. Significantly, the review also explored the reproductive benefits of GLP-1RAs, emphasizing their role in restoring ovulation and menstrual regularity. The article presented data indicating that GLP-1RAs potentially modulate the hypothalamic-pituitary-gonadal axis, leading to a reduction in serum testosterone levels and an increase in ovulation rates. Clinical trials cited within the paper supported these claims, showing improved menstrual cyclicity and enhanced fertility outcomes in women with PCOS treated with GLP-1RAs. The review called for further research to solidify the understanding of the long-term reproductive impacts of GLP-1RAs, indicating their promising role in a multifaceted treatment approach for managing both the metabolic and reproductive challenges of PCOS. [11]