SGLT2 inhibition: efficacy and safety in type 2 diabetes treatment.

INTRODUCTION: Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) offer a new opportunity for the management of type 2 diabetes mellitus. These agents reduce hyperglycemia by decreasing the renal glucose threshold and thereby increasing urinary glucose excretion. Subsequent reduction of glucotoxicity improves beta-cell sensitivity to glucose and tissue insulin sensitivity. AREAS COVERED: This article analyzes the efficacy and safety data of canagliflozin, dapagliflozin and empagliflozin in randomized controlled trials of 24 - 104 weeks duration, compared with placebo or an active comparator, in patients treated with diet/exercise, metformin, dual oral therapy or insulin. EXPERT OPINION: SGLT2 inhibitors significantly and consistently reduce glycated hemoglobin, with a minimal risk of hypoglycemia. The improvement of glucose control is similar or slightly better compared with metformin, sulfonylureas or sitagliptin, with the add-on value of significant reductions in body weight and blood pressure. However, caution is recommended in fragile elderly patients and patients with chronic kidney disease. An increased risk of genital mycotic infections is observed, but urinary tract infections are rare. Concern about an unexpected risk of euglycemic ketoacidosis has been recently reported. A possible renal protection deserves further attention. A remarkable reduction in cardiovascular mortality was reported in EMPA-REG OUTCOME with empagliflozin.