Objective:

To determine the comparative metabolic efficacy of GLP-1 receptor agonists, metformin, and myoinositol in improving metabolic outcomes among women with PCOS.

Approach:

• Study Design: Systematic review and network meta-analysis of randomized controlled trials (RCTs) following PRISMA-NMA guidelines.
• Participants: Non-menopausal women with PCOS.
• Interventions: GLP-1 receptor agonists, metformin, or myoinositol (± folic acid) versus placebo or active comparators.
• Outcomes: Primary outcome was body weight change; secondary outcomes included BMI, waist circumference, and HOMA-IR.
• Analysis Method: Frequentist random-effects NMA and CINeMA framework for assessing certainty.

Key Findings:

• GLP-1 + metformin was the most effective intervention for weight reduction (MD −5.58 kg; 95% CI −8.57 to −2.59) and BMI decrease (MD −2.17; 95% CI −2.77 to −1.58).
• GLP-1 monotherapy also showed significant decreases in weight (MD −5.22 kg) and BMI (MD −2.00).
• Waist circumference was significantly reduced by GLP-1 alone (MD −4.70 cm).
• No interventions showed significant effects on HOMA-IR.

Interpretation:

The findings suggest that the combination of GLP-1 receptor agonists and metformin may provide superior metabolic benefits compared to either treatment alone. The significant reductions in body weight and BMI with GLP-1 receptor agonists indicate their potential role in managing obesity-related complications in women with PCOS. However, the lack of significant effects on HOMA-IR highlights the need for further investigation into the impact of these interventions on insulin resistance.

Limitations:

• The analysis did not evaluate reproductive, endocrine, and patient-centered outcomes.
• No claims of overall superiority in PCOS management can be made based on the findings.
• Further long-term and head-to-head RCTs are needed including a broader range of outcomes.

Conclusion:

In conclusion, while GLP-1 receptor agonists, particularly in combination with metformin, demonstrate promising effects on weight and BMI in women with PCOS, further research is warranted to explore their long-term efficacy and safety, as well as their impact on other important outcomes related to PCOS management.

Sources:

• Systematic Review Registration