A holistic view of SGLT2 inhibitors: From cardio-renal management to cognitive and andrological aspects

Abstract

Type 2 diabetes mellitus (T2DM) is a multifactorial disease associated with complications that significantly affect both survival and quality of life, including cardiovascular, renal, cognitive, sexual, and reproductive dysfunctions. Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) have emerged as a transformative class of drugs, demonstrating benefits that extend beyond glycemic control. Large clinical trials have shown that SGLT2is reduce hospitalization for heart failure by 25-35% and slow progression of chronic kidney disease by 30-45%, with variation based on the specific agent, dose, and patient population. This narrative review examines not only these well-established benefits but also emerging evidence regarding their effects in less-explored domains. SGLT2is have been associated with improved cognitive performance, potentially through reductions in neuroinflammation and oxidative stress. In the sexual and reproductive domains, studies in men with diabetes mellitus suggest potential benefits of SGLT2is in improving erectile function, sperm motility, and testosterone levels, likely mediated by antioxidant and anti-inflammatory mechanisms. By integrating current evidence across multiple systems, this review emphasizes the role of SGLT2is in a holistic, multidisciplinary approach to the management of patients with T2DM.

Keywords: Dementia; Diabetes mellitus; Empagliflozin; Erectile dysfunction; Heart failure; Kidney failure; Male infertility; Myocardial infarction; SGLT2is.