The Effect of Oral Antidiabetic Drugs on Improving the Endocrine and Metabolic States in Women with Polycystic Ovary Syndrome: A Systematic Review and Network Meta-analysis

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrine condition in women, impacting several aspects of a woman's life, including reproductive, mental, cardiovascular, and metabolic health. Antidiabetic drugs may have beneficial effects on the endocrine and metabolic states in women with PCOS.ObjectiveThis study aimed to compare the effects of oral antidiabetic drugs on reproductive hormones, metabolic and anthropometric markers, and menstrual frequency, in patients with PCOS using network meta-analysis.MethodsPubMed, EMBASE, and CENTRAL were searched for studies published up to May 31, 2021. Randomised clinical trials enrolling participants with PCOS were included, for which sodium-glucose cotransporter 2 (SGLT-2) inhibitors, metformin (Met), dipeptidyl peptidase 4 (DPP-4) inhibitors, alpha-glucosidase inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RAs), and thiazolidinediones (TZDs) (alone or in combination) were compared with either each other, placebo, or no treatment. A network meta-analysis using a Bayesian approach was performed. The outcomes included changes in endocrine outcomes, metabolic results, menstrual frequency, and anthropometric findings. All research was conducted according to a protocol registered in the PROSPERO database (CRD42021248314).ResultsIn total, we retrieved 3383 studies, of which 47 articles enrolling 2626 participants were included for the network meta-analysis. In comparison to the control groups, Met (MD − 0.41, 95% CI − 0.73 to − 0.09) was more beneficial in reducing serum total testosterone, and GLP-1RAs+Met (MD − 5.44, 95% CI − 10.06 to − 0.89) reduced free androgen index (FAI) more effectively. Thiazolidinediones (MD 9.33, 95% CI 0.15 to 17.99) had a greater effect on sex hormone-binding globulin (SHBG) than Met. For decreasing androstenedione, Met (MD − 1.87, 95% CI − 2.73 to − 1.01), DPP-4 inhibitors (MD − 2.64, 95% CI − 4.77 to − 0.49), GLP-1RAs (MD − 3.06, 95% CI − 5.53 to − 0.62), and GLP-1RAs+Met (MD − 2.97, 95% CI − 5.85 to − 0.09) were more effective than TZDs. The confidence in evidence was often low or very low.ConclusionsIn this network meta-analysis, GLP-1 receptor agonists in combination with metformin appear to be preferable for improving hyperandrogenaemia. Metformin and TZDs offer the added benefit of improving fasting blood glucose (FBG) and low-density lipoprotein-cholesterol (LDL-C) when compared to the control groups. Metformin combined with GLP-1 receptor agonists or TZDs could be associated with a beneficial effect on menstrual recovery.