The current role of SGLT2 inhibitors in type 2 diabetes and beyond: a narrative review

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2is, gliflozins), the most recent oral antihyperglycaemic agents, provide a cardiorenal protection, an effect independent of their glucose-lowering potency. AREAS COVERED: The antihyperglycaemic potency of SGLT2is was compared with that of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists, especially when added to metformin monotherapy. Main results of cardiovascular/renal outcome trials with SGLT2is were summarized in different populations: patients with type 2 diabetes mellitus (T2DM) with or without established cardiovascular disease, patients (with or without T2DM) with heart failure (with reduced or preserved left ventricular ejection fraction) and in patients (with or without T2DM) with chronic kidney disease (CKD, including stage 4). Original papers and meta-analyses of these different trials have consistently reported a reduction in hospitalization for heart failure (alone or combined with cardiovascular mortality) and a reduced progression of CKD, with an overall good safety profile. EXPERT OPINION: Global use of SGLT2is has increased over time but remains suboptimal despite clinically relevant cardiovascular and renal protection, particularly in patients most likely to benefit. SGLT2is has proven both positive benefit-risk balance and cost-effectiveness in at risk patients. New prospects are expected in other complications, i.e. metabolic-associated fatty liver disease and neurodegenerative disorders.