SGLT2 Inhibitors and the Mechanisms Involved in Weight Loss

Purpose of Review To study the mechanisms of weight loss with inhibitors of SGLT2 receptors. SGLT2 inhibitors are a new class of drugs used in the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit the SGLT2 receptor in the proximal tubule, responsible for 90% of renal glucose reabsorption. Recent Findings SGLT2 inhibitor treatments can result in an average reduction in body weight between 2 and 4 kg; this reduction is consistent in all studies, for all molecules, either as monotherapy or in combination with other antidiabetic drugs. It is observed that weight loss is maintained for up to 4 years. Among the mechanisms proposed for weight loss are urinary glucose loss, alteration of the insulin/glucagon ratio with increased lipolysis, activation of the AMPK enzyme, inhibition of mTORC1, improvement of mitochondrial function, polarization of macrophages from M1 to M2, browning adipose tissue, leptin inhibition and increased adiponectin expression, and activation of FGF-21 expression. Summary Despite the numerous mechanisms proposed for weight loss with SGLT2 inhibitors, lipolysis seems to be the central point of all of them. It is necessary to establish how these mechanisms interact, the chronology of these changes, which one is the most important for weight loss, and how these mechanisms can contribute to the cardiovascular benefits of SLGT2 inhibitor therapy.