Role of Sodium–Glucose Cotransporter-2 Inhibitors in Managing Polycystic Ovary Syndrome: A Systematic Review

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) can improve metabolic parameters and significantly reduce weight and fat mass.Evidence regarding the use of SGLT2i in polycystic ovary syndrome (PCOS) is limited.The current systematic review compared the efficacy of SGLT2i with placebo or other active comparators in PCOS.Methods: Randomized controlled trials (RCTs) involving patients with PCOS who are overweight and obese and receiving SGLT2i as intervention and placebo or any non-hormonal comparator as controls were identified through electronic databases.The outcomes of interest included changes in metabolic, hormonal, anthropometric and body composition parameters.Results: Five RCTs involving 269 participants were included.Canagliflozin, empagliflozin, dapagliflozin and licogliflozin were studied either as monotherapy or in combination with metformin or exenatide.SGLT2i reduced insulin resistance, as evidenced by decreased homeostatic model assessment for insulin resistance and insulin and fasting plasma glucose levels.Reductions in body weight, body mass index, waist circumference and total body fat were observed with most of the SGLT2i.A reduction in dehydroepiandrosterone sulphate (DHEAS) levels was also observed in two RCTs, whereas a decrease in total testosterone level or free-androgen index was not associated with most SGLT2i.Improvements in menstrual irregularity and hirsutism scores were observed.Triglycerides were reduced, while low-density lipoprotein level was slightly increased with SGLT2i in most RCTs.Improvements in body composition and metabolic parameters were most prominent with a combination of SGLT2i with a glucagon-like peptide receptor-1 agonist (GLP1RA), while the combination of SGLT2i with metformin showed better effects on hormonal parameters.Adverse effects with SGLT2i were mostly mild and included genital infections.Conclusion: SGLT2i, when used as monotherapy or combined with metformin or GLP1RA, are a promising therapy for improving metabolic and hormonal parameters in PCOS.Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age and is characterized by hyperandrogenism, anovulation and insulin resistance (IR). 1 Women with PCOS have a high risk of developing type 2 diabetes (T2D), dyslipidaemia, hypertension and cardiovascular diseases. 2,3IR and hyperandrogenism are closely intertwined in the pathogenesis of PCOS.The current standard of care in PCOS includes combined oestrogen-progesterone tablets as first-line agents to target hyperandrogenism. 4The use of insulin-sensitizing medications reduces not only IR and metabolic abnormalities but also androgen levels and improves ovulation rates. 5tformin is recommended as the agent of choice for metabolic complications in patients with PCOS.However, its effect on body weight and body composition is minimal.In addition, a meta-analysis showed that metformin failed to reduce fasting blood glucose or insulin levels, indicating the fact that it did not significantly improve insulin sensitivity in women with PCOS who are non-diabetic and overweight. 6dium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) are anti-diabetic agents that lower blood glucose levels by increasing renal glucose excretion.SGLT2i also cause weight loss, with favourable changes in body composition, and reduce cardiovascular events in patients with and without diabetes. 7,8Thus, they appear to be promising agents for patients with PCOS.However, to date, there is limited evidence regarding the use of SGLT2i in PCOS.Two meta-analyses have shown their effectiveness in improving metabolic and hormonal parameters; however, these studies have included heterogeneous trials with different durations and outcomes. 9,10The current systematic review aims to