Cardiovascular Effects of Sodium-Glucose Cotransporter-2 Inhibitors in Adults With Type 2 Diabetes

Adults with type 2 diabetes mellitus can benefit from pharmacotherapies that lower their risk for cardiovascular disease. This review describes the salient findings from sodium-glucose cotransporter-2 (SGLT2) inhibitor cardiovascular outcome trials that serendipitously revealed the cardiorenal benefits of SGLT2 inhibitors in adults with type 2 diabetes mellitus who either have established cardiovascular disease or multiple cardiovascular risk factors. It also summarizes the findings from other phase 3 clinical studies that measured the cardiovascular effects of SGLT2 inhibitors and real-world evidence reports that compared the cardiovascular impact of SGLT2 inhibitors with other antihyperglycemic agents. The collective data indicate that SGLT2 inhibitors are pleiotropic agents that offer important cardiovascular, metabolic and renal benefits beyond glucose lowering with low incidences of hypoglycemia. Specifically, the placebo-controlled SGLT2 inhibitor cardiovascular outcome trials documented either fewer major adverse cardiac events (nonfatal myocardial infarction, nonfatal stroke and cardiovascular death) or a reduction in the composite endpoint of cardiovascular death or hospitalization for heart failure in participants with type 2 diabetes mellitus and established cardiovascular disease. Amongst those with type 2 diabetes mellitus who did not have established cardiovascular disease but did present with multiple risk factors, SGLT2 inhibitors lowered the combined endpoint of cardiovascular death or hospitalization for heart failure but had little impact on the occurrence of major adverse cardiac events. Ongoing clinical trials and subanalyses of the trials that have been reported should shed further light on the clinical benefits and utility of SGLT2 inhibitors.