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.

Background: Polycystic 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.

Objective: This 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.

Methods: PubMed, 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).

Results: In 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.

Conclusions: In 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.