The glucosuria induced by SGLT2 inhibitors (50–100 grams/day) has an equivalent loss of energy in the urine of 200–400 kcal/day.7 This energy loss triggers an increase in caloric intake that limits weight loss to 2–4 kg.7 Two-thirds of the weight loss is fat mass and one-third is fat-free mass.66 SGLT2 inhibitors induce weight loss in patients with and without diabetes and decrease fat in soft tissue compartments: visceral, subcutaneous, hepatic, and epicardial.70,71,74,75 This drug class also decreases lean and skeletal muscle mass.69 The gene discussed is SLC5A2; the disease is diabetes mellitus.