Abstract Body (Do not enter title and authors here): BACKGROUND
Type 2 diabetes mellitus (T2DM) and autoimmune diseases are independent risk factors for cardiovascular disease. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) and Glucagon-like-peptide-1 agonists (GLP1a) have shown cardiovascular benefits. This study compared the cardiovascular impacts of these medications in patients with autoimmune disease and T2DM.

METHODS
In May 2024, we queried the TriNetX Global collaborative network across 120 healthcare organizations for adults ≥18 yo diagnosed with T2DM and any of 28 autoimmune (15 connective tissue and 13 organ-specific) diseases between 01/01/05 and 06/30/23. We created 3 cohorts based on at least 3 months of SGLT2i use alone or GLP1a use alone, or neither SGLT2i nor GLP1a use during the study period (control). We conducted propensity score matching (PSM) for over 30 covariates and compared outcomes between cohorts. Cox Model analysis was used to calculate the hazard ratios (HR), 95% confidence intervals (CI), and log-rank p-values at five years.

RESULTS
In the control cohort, we identified 692,259 eligible patients, 49,458 patients on GLP1a, and 25,002 patients on SGLT2i. Compared to the control cohort, the SGLT2i cohort had a 28% lower risk of the primary composite outcome (HR 0.72; 95% CI: 0.68 – 0.76) and reduced all-cause mortality (HR 0.59; 0.56 – 0.63), acute MI (HR 0.86; 0.79 – 0.94) and ischemic stroke (HR 0.84; 0.77 – 0.91). Compared to the control cohort, the GLP1a cohort had a 28% lower risk of the primary composite outcome (HR 0.72; 95% CI: 0.69 – 0.75) as well as all-cause mortality (HR 0.54; 0.51 – 0.57), acute MI (HR 0.85; 0.80 – 0.91) and ischemic stroke (HR 0.90; 0.85 – 0.95) but higher risk of gastroparesis (HR 1.24; 1.12 – 1.38). We observed lower risks of cardiac arrest, heart failure, venous thromboembolism (VTE), adverse renal outcomes, and hospitalizations in both SGLT2i and GLP1a cohorts compared to controls.
Further analysis between the SGLT2i and the GLP1a cohorts revealed lower risks of heart failure, acute kidney injury, end-stage renal disease (ESRD), or dialysis dependence in the SGLT2i cohort but higher risks for ventricular arrhythmias, and diabetic ketoacidosis. Wrist sprain was used as a falsification endpoint.

CONCLUSION
Among patients with T2DM and autoimmune disease, SGLT2i and GLP1a use correlated with a significant reduction in cardiovascular morbidity and all-cause mortality and were associated with a reduced risk of renal failure, VTE, and hospital admission.