SGLT2 Inhibitor Cardiovascular Outcomes Trials: What the Data Show

In "SGLT2 Inhibitor Cardiovascular Outcomes Trials: What the Data Show," Dr. Vaduganathan walks through the cardiovascular outcomes trials that built the evidence base for SGLT2 inhibitors.

Dr. Vaduganathan maps the cardiovascular outcomes trial landscape behind SGLT2 inhibitors. He names four dedicated trials: EMPA-REG OUTCOME for empagliflozin, the CANVAS program for canagliflozin, DECLARE-TIMI for dapagliflozin, and VERTIS-CV for ertugliflozin. He adds a fifth line of evidence, the SCORED and SOLOIST trials, which studied the SGLT1/2 inhibitor sotagliflozin in distinct cardio-kidney-metabolic populations. Each trial enrolled a different population and tested somewhat different endpoints, he explains. EMPA-REG OUTCOME studied a very high-risk group with type 2 diabetes and established atherosclerotic cardiovascular disease, while DECLARE-TIMI enrolled a broader population defined by either multiple cardiovascular risk factors or established atherosclerotic disease. Those differences in risk profile, Dr. Vaduganathan notes, explain much of the variation in event rates across the trials.

He argues that the bigger story is not the subtle differences in point estimates but the remarkable consistency across endpoints once the trials are considered together. Meta-analysis shows consistent reductions in major adverse cardiovascular events, including myocardial infarction, stroke, and cardiovascular death, alongside substantial reductions in heart failure hospitalization and a more modest but still meaningful slowing of kidney disease progression. Dr. Vaduganathan says this consistency, more than any single trial's specific result, supports the conclusion that SGLT2 inhibitors reliably improve cardiovascular and kidney outcomes in high-risk patients with type 2 diabetes.

He also addresses whether these benefits reflect a class effect or a drug-specific one, concluding that the evidence points toward a class effect for major outcomes. That said, he still favors the individual agents actually studied in a given population, noting that empagliflozin and dapagliflozin carry the strongest evidence base in heart failure specifically, which is why he reaches for those two agents when treating that population in his own practice.

Up next, in "SGLT2 Inhibitors as a Class Effect: Payer and Formulary Considerations," Dr. Vaduganathan shifts to how payers should interpret that trial evidence when setting formulary policy.