SGLT-2 inhibitors reduced risk of cardiovascular disease, death, review finds

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduced risk of cardiovascular disease and death in patients with diabetes whether or not the patients had established cardiovascular or kidney disease, according to a recent systematic review.

Researchers conducted a systematic review and meta-analysis of four large trials comparing SGLT-2 inhibitors with placebo in patients with diabetes. The four trials reported effects on cardiovascular outcomes overall and for subgroups of patients with baseline cardiovascular disease, reduced kidney function, and heart failure. Results were published Jan. 29 by the Journal of the American Heart Association.

There were 38,723 patients with a median of 2.9 years of follow-up: 22,870 (59%) had cardiovascular disease, 7,754 (20%) had reduced kidney function, and 4,543 (12%) had heart failure. There were 3,828 major adverse cardiac events, 1,192 hospitalizations for heart failure, 1,506 cardiovascular deaths, and 2,612 deaths from any cause. Overall, the review found a significant reduction in major adverse cardiac events with the drug class (hazard ratio, 0.88; 95% CI, 0.82 to 0.94; P<0.001). There was no evidence that the observed benefits of SGLT-2 inhibitors varied by subgroup, defined by the presence of cardiovascular disease or heart failure at baseline (all P>0.252 for interaction; I²<25%).

All patient subgroups saw benefit on the outcomes of hospitalization for heart failure (all P>0.302 for interaction; I²<10%), cardiovascular death (all P>0.167 for interaction; I²<50%), and death from any cause (all P>0.354 for interaction; I²=0%). The study found one difference in effects across subgroups. SGLT-2 inhibitors were associated with reduced risk for stroke among patients with reduced kidney function but not those with preserved kidney function (P=0.020 for interaction; I²=81%).

“The broad constancy of the findings across subgroups suggests wide clinical utility for the drug class,” the authors wrote. They said that “a broad range of patients” with type 2 diabetes could likely benefit from the drug class. “Our results call for a reevaluation of current guideline recommendations for SGLT-2 inhibitor therapy, with a view to include those with and without established [cardiovascular disease],” they wrote. The authors did caution that low event rates among the study patients without cardiovascular disease at baseline led to low statistical power in the findings among that subgroup.