Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may benefit many patients with type 2 diabetes—not just those with established atherosclerotic cardiovascular disease (ASCVD), according to new research published online ahead of print in The Lancet.

Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital in Boston, and colleagues conducted a meta-analysis of 34,322 patients from the EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58 randomized controlled trials. Of these, 60.2% had ASCVD and 39.8% had multiple risk factors for it. During follow-up, 3342 major adverse cardiovascular events (MACE), 2028 cardiovascular deaths or heart failure hospitalizations, and 766 renal composite outcomes occurred.

SGLT2i (e.g., empagliflozin, canagliflozin, and dapagliflozin) significantly reduced the composite risk for myocardial infarction, stroke, and cardiovascular death by 11% overall, but benefits were seen only in patients with established ASCVD. However, patients with and without ASCVD or heart failure treated with SGLT2i experienced a significant 23% lower risk of cardiovascular death or heart failure-related hospitalization.

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With respect to renal outcomes, SGLT2i significantly cut the risk of renal disease progression (defined as declining estimated glomerular filtration rate, end-stage renal disease, or renal death) by 45% regardless of ASCVD status. Patients with more severe kidney disease at baseline experienced greater reductions in heart failure-related hospitalizations but lesser reductions in progression of renal disease.

“These data suggest that SGLT2i should be considered in patients with type 2 diabetes regardless of presence of atherosclerotic cardiovascular disease or history of heart failure, given that SGLT2i safely reduce HbA1c and reduce the risk of hospitalisation for heart failure and progression of renal disease across a broad spectrum of patients with type 2 diabetes,” Dr Sabatine’s team wrote.

With regard to adverse events, the studies included in the meta-analysis as well as a recent BMJ study associated SGLT2i with increased risks for amputations and diabetic ketoacidosis.

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Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. DOI:10.1016/S0140-6736(18)32590-X (Published online November 10, 2018)

Ueda P, Svanström H, Melbye M, et al. Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ 2018;363. DOI:10.1136/bmj.k4365 (Published online November 14, 2018)