Abstract Body (Do not enter title and authors here): Introduction:
Immune checkpoint inhibitors (ICI) can trigger cardiac-related immune adverse effects by activating T cells against myocardial self-antigens, which can cause myocarditis, arrhythmias, and cardiomyopathy. SGLT2 inhibitors have anti-inflammatory properties and can help regulate immune cells, which might play a role in preventing immune related cardiac adverse events in patients on ICI.

Study Aim
To evaluate SGLT2 inhibitor impact on preventing major adverse cardiovascular events in patients receiving ICI

Methods:
This retrospective cohort study utilized the TrinetX Global Collaborative Network to analyze patients aged ≥ 18 from January 2014 and May 2025. Two cohorts were identified: cohort 1 included patients receiving ICI in combination with SGLT2 inhibitors, and cohort 2 received ICIs without SGLT2 inhibitors. Both cohorts excluded individuals with cardiomyopathy or heart failure (HF). The outcomes assessed were HF, atrial fibrillation/flutter (AF), acute myocardial infarction (AMI), myocarditis, and mortality. Absolute risk, relative risk (RR), 95% confidence interval (CI), and p-value were calculated using TrinetX platform. Kaplan-Meier analysis was used to estimate survival probabilities and log-rank tests to compare the survival curves.

Results:
After propensity score matching, both cohorts had 2,862 patients with mean age at index diagnosis 68 with 35% females and 62% males. SGLT-2 group had 0% incidence of heart failure vs 1.103% in control group with a p-value of < 0.0001, and RR being 0 as there were no events in cohort 1. There was lower risk of AF in SGLT-2 group compared to non-user group (RR 0.7, 95% CI: 0.535-0.916, p-value 0.009). The risk of AMI (RR 0.85, 95% CI: 0.592-1.212, p-value 0.3625) and myocarditis (RR 1.001, 95% CI: 0.417-2.401, p-value 0.998) was similar between both groups. All-cause mortality was lower in SGLT-2 inhibitor group compared to control group (RR 0.658, 95% CI: 0.613-0.706, p-value < 0.0001)

Conclusion:
SGLT2 inhibitors were associated with a lower incidence of HF, AF, and all-cause mortality in patients receiving ICIs, with no significant impact on AMI or myocarditis. Further studies are needed to explore the potential benefits of SGLT2 inhibitors for primary prevention of major adverse cardiovascular events in this patient population.