Weight loss associated with sodium-glucose cotransporter-2 inhibition: a review of evidence and underlying mechanisms

With their novel, insulin-independent mechanism, sodium-glucose cotransporter-2 (SGLT2) inhibitors are a major turning point in the management of type 2 diabetes mellitus. At present, there are several SGLT2 inhibitors available or in development, and these oral anti-hyperglycaemic agents lower plasma glucose through the inhibition of SGLT2-mediated reuptake of filtered glucose in the kidney. This unique mechanism of action is also expected to result in other beneficial effects, such as weight loss and blood pressure reduction. In various studies, including randomized controlled trials and real-world studies, patients treated with SGLT2 inhibitors have reported weight loss of around 1 to 3 kg. This review describes the characteristics of weight loss associated with SGLT2 inhibitor therapy, the clinical factors affecting SGLT2 inhibitor-associated weight loss and the possible underlying mechanisms of SGLT2 inhibitor-associated weight loss, including changes in metabolism and body composition, and the role of a reduction in insulin dose and compensatory hyperphagia. Understanding the weight loss effect of SGLT2 inhibitors, its related factors and underlying mechanisms can aid clinicians in optimal treatment decision-making, provide valuable insight on both obesity and diabetes management and reveal areas of future research and new therapeutic options.