What is the role of semaglutide (glucagon-like peptide-1 receptor agonist) in the treatment of polycystic ovary syndrome (PCOS)?

Semaglutide for PCOS Treatment

Semaglutide appears to be effective for PCOS management in women with obesity, demonstrating significant benefits for weight reduction, metabolic parameters, and hormonal regulation, though it is not yet officially approved specifically for PCOS treatment. 1, 2

Current Evidence and Efficacy

• Semaglutide is among the most potent long-acting GLP-1 receptor agonists (GLP-1 RAs), showing superior results compared to shorter-acting agents like exenatide in PCOS patients 1
• In obese PCOS patients unresponsive to lifestyle modifications, semaglutide treatment (0.5 mg weekly) resulted in significant weight loss (mean 7.6 kg after 3 months), with nearly 80% of patients achieving at least 5% weight reduction 2
• Continued treatment for 6 months showed progressive benefits with mean weight loss of 11.5 kg and BMI reduction from 34.4 to 29.4 in responsive patients 2
• GLP-1 RAs demonstrate greater efficacy for weight loss and insulin resistance improvement compared to metformin in overweight/obese women with PCOS 3

Metabolic and Hormonal Benefits

• Semaglutide treatment in PCOS patients improves insulin sensitivity with decreased basal insulin values and improved HOMA-IR, even in patients who don't achieve significant weight loss 2
• GLP-1 RAs significantly reduce waist circumference (mean difference: -5.16 cm), BMI (mean difference: -2.42), serum triglycerides (mean difference: -0.20), and total testosterone levels (mean difference: -1.33) compared to placebo 4
• Semaglutide delays gastric emptying in women with PCOS and obesity, which contributes to reduced food intake and improved glycemic control 5

Reproductive Benefits

• 80% of PCOS patients responsive to semaglutide (achieving >5% weight loss) experienced normalization of menstrual cycles after 6 months of treatment 2
• Even modest weight loss of 5% can significantly improve both metabolic and reproductive abnormalities in PCOS 1
• GLP-1 RAs have shown potential to improve fertility with enhanced ovulation and pregnancy rates in obese women with PCOS 6

Limitations and Considerations

• Current evidence on semaglutide for PCOS is limited, with only one small pilot study specifically examining its effects 1
• Most studies on GLP-1 RAs in PCOS used suboptimal medication doses and short treatment durations (12 weeks), limiting the ability to demonstrate changes in important clinical outcomes like hirsutism and fertility 1
• The 2023 International Evidence-based Guideline on PCOS notes that published data examining anti-obesity agents in women with PCOS are very limited, and further research is urgently needed 7
• All GLP-1 RAs consistently resulted in more adverse events than controls, including gastrointestinal side effects, though semaglutide studies reported relatively few side effects 1, 2

Practical Recommendations

• Semaglutide should be considered as an adjunct to lifestyle modifications in PCOS patients with obesity, particularly those unresponsive to diet and exercise alone 1, 2
• Physical activity, specifically resistance training, should accompany GLP-1 RA treatment to preserve lean body mass and promote weight maintenance 1
• Starting with lower doses (0.5 mg weekly) may help minimize side effects while still providing significant benefits for weight loss and metabolic parameters 2
• Treatment should be continued for at least 6 months in responsive patients to maximize benefits for weight loss and menstrual regularity 2

Research Gaps

• More high-quality, multicenter studies of semaglutide in PCOS are urgently needed, incorporating reproductive, metabolic, and psychological outcomes 1
• The role of anti-obesity agents in PCOS management should be a high priority for future research according to the 2023 International Evidence-based Guideline 7