Cardiovascular benefits of SGLT2i in type 2 diabetes without heart failure: a subgroup analysis

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are proven to reduce cardiovascular death and the risk of major adverse cardiovascular events (MACE) in patients with a diagnosis of heart failure. The real-world benefits of SGLT2i in patients with type 2 diabetes mellitus (DM) without a prior diagnosis of heart failure among insulin users versus non-users are unknown. Objective To improve understanding of the morbidity and mortality benefit of SGLT2i among patients with T2DM without heart failure. Methods We performed a retrospective cohort study using a de-identified national database with over 113 million patients (TriNetX Research Network, Cambridge, MA; IRB exempt). We identified all adult patients (≥18 years) diagnosed with DM on or after January 1st 2014. We excluded patients with a diagnosis of heart failure, acute myocardial infarction or cerebral infarction and then stratified patients into groups by use of insulin and SGLT2i. We examined the outcomes of acute myocardial infarction, coronary revascularization, cerebral infarction, and cardiovascular death after index diagnosis. We performed a 1:1 greedy nearest neighbor propensity score matching to balance cohorts on age, race, and traditional risk factors for cardiometabolic disease. Estimates of risk ratios and 95% confidence intervals (CI) were used to describe outcome risks. P-values of <0.05 were considered statistically significant. Results Using the TriNetX database, we identified a total of 625,030 propensity score matched patients with DM using insulin. Of these patients, those on SGLT2i (50%), 18.6% had incident MACE versus 28.3% among those not on SGLT2i with a risk ratio of 0.66 (95% CI 0.651, 0.664). Of the 460,232 patients in the propensity matched cohort of patients with DM without insulin use, those on SGLT2i therapy (50%) had a lower risk of MACE of 4.8% compared to 9.4% among those without SGLT2i use (risk ratio of 0.51, 95% CI 0.497, 0.520). Conclusion Insulin use is associated with higher risk of MACE compared with no insulin use. SGLT2i are associated with reduced MACE in patients with DM without a history of heart failure both among those with and without the use of insulin. All patients with diabetes may benefit from the inclusion of an SGLT2i in their regimen to reduce their risk of future cardiovascular events.