Abstract / Summary
Background: Cardiovascular disease (CVD) remains the predominant cause of morbidity and mortality among patients with type 2 diabetes (T2DM). While randomized controlled trials (RCTs) have established cardiovascular (CV) and renal benefits of SGLT2i and GLP-1 RAs, translating these findings into everyday clinical practice requires evidence from real-world observational studies, which better reflect heterogeneous patient populations, comorbidities, adherence, and treatment patterns. Objective: To review and synthesize available real-world evidence from observational, registry-based, and cohort studies evaluating cardiovascular outcomes associated with SGLT2i and GLP-1 RA use in T2DM (with or without established CVD or heart failure). Key Findings: Observational data support significant benefits of SGLT2i in reducing heart-failure hospitalizations, all-cause mortality, and composite cardiovascular events; in some cohorts, addition of GLP-1 RA to SGLT2i further reduced mortality and hospitalization risk. Comparative analyses of SGLT2i vs GLP-1 RA show variable results — SGLT2i often show stronger benefit in heart-failure–related outcomes, while GLP-1 RA may be competitive or superior in certain atherosclerotic / MACE endpoints depending on baseline patient risk. Underutilization of these agents in high-risk patients remains a pervasive concern. Conclusion: Real-world evidence largely confirms the cardioprotective effects observed in RCTs, and supports a patient-tailored approach when choosing between SGLT2i and GLP-1 RA therapy. However, important gaps remain, including the need for more data in under epresented populations, post-acute coronary syndrome settings, and long-term safety of combination therapy.