SGLT2 inhibitors and GLP-1 receptor agonists: impact on mortality in diabetic patients with cardiovascular disease

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to reduce cardiovascular risk and mortality in patients with type 2 diabetes mellitus (T2D), yet remain underutilized in clinical practice. This study aimed to evaluate real-world treatment patterns and associated mortality outcomes among patients with T2D and established atherosclerotic cardiovascular disease (ASCVD). Methods: The CARdiovascular and DIABetes (CARDIAB) cohort included 138,397 patients with T2D and ASCVD. Patients were categorized into four treatment groups: (i) both SGLT2-I and GLP-1RA, (ii) SGLT2-I only, (iii) GLP-1RA only, and (iv) neither medication. The primary outcome was all-cause mortality. Results: Of the 138,397 patients, 57% received neither SGLT2-I nor GLP-1RA, 17% received both, 20% received SGLT2-I only, and 6% received GLP-1RA only. Female sex, older age, non-coronary ASCVD, and absence of follow-up in specialized cardiology or diabetes clinics were associated with lower treatment rates. Compared to those receiving neither medication, all-cause mortality was significantly lower among patients treated with SGLT2-I only (HR 0.28, 95% CI 0.27–0.29), GLP-1RA only (HR 0.39, 95% CI 0.37–0.40) and both agents (HR 0.17, 95% CI 0.16–0.18). This association remained significant following a multivariate analysis. Conclusion: In patients with T2D and ASCVD, treatment with SGLT2-I and GLP-1RA, especially in combination, is associated with a substantial reduction in mortality. These findings highlight significant gaps in implementation and the urgent need to optimize use of evidence-based therapies in this high-risk population.