Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in Overweight Women With PCOS

OBJECTIVE: To evaluate the efficacy of insulin sensitizers on menstrual frequency, sex hormone, and metabolic parameters in overweight women with polycystic ovary syndrome (PCOS). METHODS: We searched multiple databases from inception to September 2019 for randomized controlled trials. Network meta-analysis was conducted using multivariate random effects method. RESULTS: Fourteen trials reporting on 619 women were included. Compared with metformin, metformin + thiazolidinediones (TZDs) was more superior in menstrual recovery (weighted mean difference [WMD] 3.68; 95% credibility interval [CrI], 1.65 to 8.20), metformin + glucagon-like peptide-1 (GLP-1) receptor agonists was more effective in decreasing androstenedione (WMD −2.53; 95% CrI, −3.96 to −1.09), both metformin + GLP-1 receptor agonists (WMD 9.22; 95% CrI, 5.46 to 12.98) and metformin + TZDs (WMD 4.30; 95% CrI, 0.78 to 7.82) were more effective in increasing sex hormone–binding globulin (SHBG), while TZDs were less effective in decreasing body mass index (BMI) (WMD 1.69; 95% CrI, 0.72 to 2.66). Compared with GLP-1 receptor agonists, metformin + GLP-1 receptor agonists was associated with higher SHBG (WMD 7.80; 95% CrI, 4.75 to 10.85), lower free testosterone (WMD −1.77; 95% CrI, −3.25 to −0.29), lower androstenedione (WMD −2.70; 95% CrI, −3.91 to −1.50) and lower fasting blood glucose (WMD −0.41; 95% CrI, −0.73 to −0.08). CONCLUSION: For overweight women with PCOS, both metformin combined with GLP-1 receptor agonists and metformin combined with TZDs appear superior to monotherapy in improving hyperandrogenemia. Metformin combined with TZDs could be particularly effective in promoting the recovery of menstruation. Metformin combined with GLP-1 receptor agonists has the additional advantage of improving fasting glucose when compared with GLP-1 receptor agonists alone. TZDs are inferior to metformin in decreasing BMI.