Efficacy of Canagliflozin versus Metformin in Women with Polycystic Ovary Syndrome: A randomized, open label, non-inferiority trial.

Objectives This study aimed to determine the safety and efficacy of canagliflozin in comparison to metformin in polycystic ovary syndrome (PCOS) patients with insulin resistance (IR). Methods A single center, prospective, randomized open-label (ratio 1:1) non-inferiority trial was conducted at the Department of Endocrinology, Shanghai Tenth People's Hospital, between July 2019 and April 2021. Women aged 18-45 years with PCOS and IR were enrolled and randomly assigned to either 100 mg (n = 33) canagliflozin daily or 1500-2000 mg metformin daily (n = 35) for 12 weeks. The primary outcome was changes in homeostatic model assessment (HOMA)-IR after 12 weeks of treatment. The secondary outcomes included changes in anthropometric measurements, menstrual frequency, sex hormone levels, metabolic parameters, and body fat distribution. Results For lowering of HOMA-IR after 12 weeks of treatment, canagliflozin was found to be non-inferior to metformin (least-squares mean difference -0.81% [95% CI: -2.13 to 0.51]). Both canagliflozin and metformin could significantly improve menstrual pattern, reduce body weight and total fat mass, and decrease triglyceride levels. Compared with metformin, canagliflozin had significant advantages in reducing uric acid and dehydroepiandrosterone sulfate levels. Pruritus vulvae (9.09%) and gastrointestinal reaction (55.55%) were the main adverse events in the metformin group and canagliflozin group, respectively. Conclusion Our study demonstrates that canagliflozin was not inferior to metformin in PCOS patients with IR, which suggests that sodium-glucose co-transporter 2 inhibitors should be considered as effective drugs in the treatment of PCOS patients with IR. This article is protected by copyright. All rights reserved.