Abstract Body (Do not enter title and authors here): Background
There is an increasing prevalence of type 2 diabetes (T2D) and systolic heart failure. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are becoming popular in the management of T2D. Previous studies have demonstrated that GLP-1 RAs reduce major adverse cardiovascular events (MACE) in T2D patients compared to placebo. However, the impact of GLP-1 RAs on mortality and cardiovascular outcomes in patients with T2D and systolic heart failure remains uncertain.

Aim
This study examines the effects of GLP-1 RA on individuals with T2D and systolic heart failure, focusing on all-cause mortality, cardiovascular outcomes (including ischemic heart disease, acute myocardial infarction, heart failure exacerbations, stroke, peripheral vascular disease, chronic kidney disease), and all-cause hospitalization.

Methods
The TriNetX research database was utilized to identify patients aged 18 years and older with T2D and systolic heart failure. Patients were classified into two groups: GLP-1 RA users and non-users. Propensity score matching (1:1) was conducted based on demographics, body mass index, comorbidities, glycated hemoglobin levels, and medications, resulting in a matched cohort of 23,873 patients. Outcomes analyzed included all-cause mortality, cardiovascular outcomes and all cause hospitalization. Survival analysis was performed using TriNetX software, estimating the probability of outcomes over 5 years from the index event and generating hazard ratios (HR), log-rank tests, and Kaplan-Meier survival curves.

Results
The GLP-1 RA user group demonstrated a reduced hazard ratio (HR, 95% confidence interval) over 5 years compared with the control group for all-cause mortality (0.705, 0.675-0.736, P <0.001), composite of cardiovascular outcomes (0.94, 0.922-0.958, P<0.001), all cause hospitalization (0.809, 0.788-0.831, P <0.001) (Figure), acute myocardial infarction (0.822, 0.790-0.857, P <0.001), and heart failure exacerbation (0.962, 0.944-0.981, P <0.001). All other individual cardiovascular outcomes also showed significant risk reductions in favor of the GLP-1 RA cohort.

Conclusion
In patients with type 2 diabetes and systolic heart failure, GLP-1 RA therapy significantly reduces mortality and cardiovascular events over a 5-year period, independent of body weight.