Long-term effectiveness of SGLT2 inhibitors in type 2 diabetes patients with myocardial injury: A population-based study

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardiovascular benefits in randomized trials. However, real-world evidence on their cardioprotective effect in high-risk populations with documented myocardial injury-such as heart failure (HF), acute coronary syndrome (ACS), myocardial revascularization, or cardiac surgery-is still limited. Objective: To evaluate the impact of SGLT2 inhibitor adherence on cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and a history of myocardial injury, in a real-world setting. Methods: We retrospectively reviewed the healthcare utilization databases of the Lombardy region (Italy) to identify all patients with T2DM who were dispensed SGLT2 inhibitors between 2014-2020, and had one hospitalization for HF, myocardial revascularization, ACS or cardiac surgery in the previous 10 years. Adherence was calculated as the proportion of days covered by therapy during follow-up. Cox regression analysis was performed to estimate the hazard ratios (HR) for cardiovascular hospitalizations and death. Results: Among 1789 HF, 5759 revascularization, 3986 ACS, and 4580 cardiac surgery patients, higher adherence to SGLT2i therapy was consistently associated with a lower risk of CV events or death. Adjusted HRs for high vs. very low adherence were: HF, 0.65 (95 %CI:0.52-0.82); revascularization, 0.70 (95 %CI:0.59-0.84); ACS, 0.76 (95 %CI:0.62-0.93); and cardiac surgery, 0.69 (95 %CI:0.57-0.84). A dose-response trend was observed across adherence levels. Conclusion: High adherence to SGLT2 inhibitors therapy can significantly decrease the risk of cardiovascular-related hospitalization and death in patients with T2DM and several forms of myocardial injury, such as HF, ACS, myocardial revascularization, and cardiac surgery.