Sodium‑glucose cotransporter‑2 inhibitors in obesity and associated cardiometabolic disorders: where do we stand?

As the tide of obesity and its complications are on the rise, there is an urgent need for new drugs with weight‑lowering and beneficial metabolic properties. Obesity‑related disorders, such as metabolic syndrome, prediabetes, type 2 diabetes (T2D), cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD) make this need more than mandatory. Sodium‑glucose cotransporter‑2 (SGLT‑2) inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) are the latest class of agents to receive approval for the treatment of T2D. Not long after their marketing, a wide spectrum of target organ‑protective and overall beneficial health effects associated with their use began to unveil. An increasing bulk of evidence indicates that these actions are to a great degree independent of glucose lowering, which has led to the broadening of the indications for SGLT‑2 inhibitors outside the frame of antihyperglycemic therapy. Additionally, their unique mode of action including increased renal glucose excretion, and hence net energy loss, could render SGLT‑2 inhibitors attractive candidates for the treatment of obesity. Very few reviews in the literature have holistically appraised the therapeutic potential of SGLT‑2 inhibitors in obesity and its associated complications. Herein, we summarize the currently available evidence regarding the effects of drugs of this class on body adiposity, together with considerations on their potential use as weight loss agents. Furthermore, we attempt to overview their actions and future perspectives of their use with respect to a range of obesity‑related disorders, which include cardiovascular, renal, and ovarian dysfunctions, as well as NAFLD and malignancy.