Effect of SGLT2 Inhibitors on Improving Glucolipid Metabolism and Reproductive Hormone Status in Overweight/Obese Women with PCOS: A Systematic Review and Meta-Analysis

Background Obesity, insulin resistance, and hyperandrogenemia are commonly seen in women with polycystic ovary syndrome (PCOS), and these three conditions form a vicious cycle leading to reproductive and metabolic abnormalities. Metformin improves the symptoms of PCOS by increasing insulin sensitivity but is not therapeutically optimal. Recent studies have reported that sodium-glucose co-transporter protein receptor inhibitors improve insulin resistance and reduce the weight of patients with PCOS. We performed a meta-analysis to assess the influence of sodium-glucose co-transporter protein-2 (SGLT2) inhibitors on anthropometric, glycolipid metabolism and reproductive outcomes after therapy of overweight/obese women with PCOS. Methods We searched the relevant literature published up to April 2023. Information on the effect of SGLT2 inhibitors on overweight/obese patients with PCOS was extracted independently by two reviewers. Review Manager 5.3 was used for meta-analysis. Results Five randomized controlled trials that met our criteria were retrieved. Our meta-analysis demonstrated that in overweight/obese patients with PCOS, SGLT2 inhibitors treatment was significantly superior to metformin treatment in terms of reducing body weight (P = 0.02, I 2 = 36%), decreasing dehydroepiandrosterone sulfate concentrations [SMD = -0.42, 95% CI (-0.76, -0.07), I 2 = 22%, P = 0.02], and reducing the incidence of nausea [RR = 0.35, 95% CI (0.21, 0.60), I 2 = 71%, P = 0.0001]. Conclusions SGLT2 inhibitors are a possible alternative therapy for treating overweight/obese women with PCOS who do not respond favorably to metformin treatment. However, further large randomized controlled trials and cost-effectiveness analyses are warranted to guide the implementation of SGLT2 inhibitors treatment in this population.