In this issue of Metabolism, Omori et al [1] report that dapagliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), prevents hepatic steatosis (assessed by triglyceride liver content) after 8 weeks of administration in db/db mice, a mouse model of obesity and diabetes.

SGLT2i represent the latest antidiabetic drug category; members of this class exert their glucose-lowering effect via inhibiting glucose reabsorption in the kidneys and thus causing glucosuria and osmotic diuresis [2]. Furthermore, these drugs have been reported to improve several cardiovascular (CV) risk factors, including fasting and postprandial plasma glucose, body weight, blood pressure, mixed dyslipidemia, and serum uric acid, as well as endothelial dysfunction, arterial stiffness and inflammation [[3],[4],[5],[6],[7]]. Apart from diuresis and the subsequent reduction in preload, SGLT2i also favour the production of ketone bodies (acting as a “superfuel” for the heart and the kidneys), block the renin-angiotensin-aldosterone-system (causing positive intropic effects and vasodilation) and the sympathetic nervous system, and downregulate the activity of the Na+–H+ exchanger in myocytes (restoring mitochondrial calcium in cardiomyocytes)[8, 9]. These mechanisms contribute to the cardiorenal benefits of SGLT2i, resulting in a reduction of CV and total mortality [10], as well as a decrease of renal causes of death and end-stage kidney disease in type 2 diabetes mellitus (T2DM) patients [11]. In contrast, the benefits of treatment with SGLT2i in terms of liver function and of possible reduction of hepatic steatosis, inflammation or fibrosis are under investigation. In the USA and Europe, there are currently 3 SGLT2i available in the market (ie canagliflozin, dapagliflozin and empagliflozin)[12], whereas ertugliflozin has also been approved for T2DM treatment (but it is not available in the market yet [13]). Furthermore, ipragliflozin, luseogliflozin and tofogliflozin are available only in Japan [14]. The main side effect of these drugs is genital infections which are mostly mild and transient. However, canagliflozin has also been linked to an increased risk of bone fractures and amputations of the lower extremities [12, 15].