GLP-1 Receptor Agonists for Secondary Prevention After Myocardial Infarction and Stroke in Type 2 Diabetes: Nationwide Real-World Evidence

Abstract Aims Glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular risk in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease and are recommended in guidelines. We evaluated the real-world effectiveness of GLP-1RA therapy on cardiovascular outcomes in patients with T2D after myocardial infarction (MI) or ischemic stroke and examined trends and disparities. Methods Using nationwide Czech registry data (2015–2024), we identified patients with incident nonfatal MI or ischemic stroke and confirmed T2D. GLP-1RA users—initiating therapy within 12 months post-event—were propensity score-matched to non-users. The primary outcome was major adverse cardiovascular events (MACE: nonfatal MI, nonfatal stroke, cardiovascular death); secondary outcomes included individual components and all-cause mortality. Results GLP-1RA therapy was initiated in only ∼2% of MI and stroke survivors with T2D. Among 126,845 MI survivors, 28,206 had T2D; the matched cohort comprised 2,271 patients (401 GLP-1RA; median follow-up 35 months). GLP-1RA use was associated with lower risk of MACE (HR:0.7; 95%CI:0.52–0.93), all-cause (HR:0.61;95%CI:0.47–0.80) and cardiovascular death (HR:0.54, 95%CI:0.36–0.80). Among 177,115 stroke survivors, 73,750 had T2D; the matched cohort comprised 2,235 patients (385 GLP-1RA; median follow-up 27 months). GLP-1RA use was associated with lower risk of MACE (HR:0.71; 95%CI:0.54–0.94), all-cause (HR:0.59;95%CI:0.46–0.76) and cardiovascular death (HR:0.55; 95%CI:0.37–0.81). Conclusions GLP-1RA therapy after MI or stroke in T2D was associated with substantially lower risks of MACE, cardiovascular and all-cause death in real-world practice. Utilization remained low, particularly among women and older adults, underscoring the need for broader and more equitable implementation in secondary prevention.