Effects of Exenatide plus Metformin versus Metformin alone on insulin resistance in women with Polycystic Ovary Syndrome: A systematic review and meta-analysis

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women, often accompanied by insulin resistance, obesity, and increased metabolic risk. While Metformin (MET) is commonly used to improve insulin sensitivity, its limited effect on postprandial glucose has led to interest in combination therapies. Exenatide (EX), a glucagon-like peptide-1 receptor agonist, may offer complementary benefits. Objective: To assess the effectiveness of EX combined with MET (EX + MET) versus MET alone (MET) in improving insulin resistance and metabolic outcomes in overweight and obese women with PCOS. Methods: This systematic review and meta-analysis included five randomized controlled trials (n = 339) and followed Preferred Reporting Items for Systematic reviews and Meta-Analysis Extension guidelines. The primary outcome was the change in insulin resistance (Homeostatic Model Assessment of Insulin Resistance [HOMA-IR]). Secondary outcomes included body mass index (BMI), 2-h oral glucose tolerance test (OGTT), lipid profile, and reproductive hormones. Results: Pooled analysis revealed that EX + MET significantly reduced HOMA-IR (mean difference [MD]: -0.9; p < 0.001), improved 2-h OGTT values (MD: -1.78; p < 0.001), reduced BMI (MD: -0.4; p = 0.03), with low heterogeneity. Combination therapy also improved triglyceride and total cholesterol levels. However, no significant effects were observed on reproductive hormones or low-density lipoprotein and high-density lipoprotein cholesterol. Conclusions: While hormonal and some lipid changes were not significant, their inclusion highlights the multifaceted impact of PCOS and the need for longer-term studies. By improving insulin sensitivity and weight-related outcomes, EX + MET may be a valuable clinical option for metabolically high-risk PCOS patients.