OP0025 MORTALITY AND MAJOR ADVERSE CARDIOVASCULAR EVENTS AFTER GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST INITIATION IN PATIENTS WITH AUTOIMMUNE DISEASES AND TYPE 2 DIABETES: A POPULATION-BASED STUDY

Patients with autoimmune rheumatic diseases are at higher risk of cardiovascular complications and premature mortality[1,2], possibly related to chronic inflammation. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are used to treat type 2 diabetes and obesity (two pro-inflammatory states associated with systemic autoimmune diseases) and have anti-inflammatory properties[4], but their clinical effects on cardiovascular outcomes and mortality in patients with autoimmune diseases remain unknown.To assess the risk of all-cause mortality and major adverse cardiovascular events (MACE) in patients with autoimmune diseases and type 2 diabetes initiating GLP-1 RAs versus dipeptidyl peptidase-4 inhibitors (DPP-4is).We performed a sequential propensity score (PS) overlap weighted population-based cohort study using administrative health data from British Columbia. Data included diagnostic codes from physician visits and hospitalizations in a universal health care system, all pharmacy-dispensed medications, and vital statistics from January 1, 2010, to December 31, 2021. All patients with an autoimmune disease (i.e., rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or a systemic autoimmune rheumatic disease) and type 2 diabetes who newly initiated a GLP-1 RA or DPP-4i were identified using ICD-9/10 codes. The primary outcome of interest was all-cause mortality. The secondary outcome was MACE (composite of cardiovascular death, myocardial infarction, and ischemic stroke). Herpes zoster reactivation was assessed as a negative control outcome. Cox proportional hazard regression models with PS overlap weighting were used.We identified 10,855 patients with autoimmune diseases and type 2 diabetes who newly initiated a GLP-1 RA or DPP-4i. All-cause mortality rate was lower among initiators of GLP-1 RAs compared to initiators of DPP-4is, with a weighted hazard ratio (HR) of 0.48 (95% CI, 0.31-0.75) and rate difference (RD) of -9.4 (95% CI, -16.0 to -2.7) per 1000 person-years (Table 1). Rates of MACE were also lower with GLP-1 RA versus DPP-4i exposure (HR 0.66 [CI, 0.50-0.88], RD -10.5 [CI, -20.4 to -0.8]). There was no difference in the risk of herpes zoster reactivation (HR 0.96 [CI, 0.65-1.43).In patients with autoimmune diseases and type 2 diabetes, GLP-1 RA exposure is associated with a lower risk of all-cause mortality and MACE compared to DPP-4i exposure. Further research is needed to explore potential adiposity-dependent and independent mechanisms through which GLP-1 RAs may reduce cardiovascular risk for patients with autoimmune rheumatic diseases.[1]Aviña-Zubieta JA, Choi HK, Sadatsafavi M, et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: A meta-analysis of observational studies. Arthritis Care Res 2008;59:1690-1697.[2]Bartels CM, Buhr KA, Goldberg JW, et al. Mortality and cardiovascular burden of systemic lupus erythematosus in a US population-based cohort. J Rheumatol 2014;41:680-7.[3]Tao Y, Ge G, Wang Q, et al. Exenatide ameliorates inflammatory response in human rheumatoid arthritis fibroblast-like synoviocytes. IUBMB Life 2019;71:969-977.Table 1.All-cause mortality and major adverse cardiovascular events (MACE) among patients with autoimmune diseases and type 2 diabetes initiating GLP-1 receptor agonists or DPP-4 inhibitors, after propensity-score overlap weightingGLP-1 receptor agonists (n=3,570)DPP-4 inhibitors (n=7,285)All-Cause MortalityEvent, number28446Mean follow-up (years)1.461.88IR, per 1000 person-years8.517.9HR (95% CI)0.48 (0.31, 0.75)1.0 (ref)RD (95% CI)-9.4 (-16.0, -2.7)ReferenceMACEEvent, number83632Mean follow-up (years)1.421.81IR, per 1000 person-years21.532.0HR (95% CI)0.66 (0.50, 0.88)1.0 (ref)RD (95% CI)-10.5 (-20.4, -0.8)Referencen, number; IR, incidence rate; HR, hazard ratio; RD, risk difference; CI, confidence interval.NIL.Derin Karacabeyli: None declared, Na Lu: None declared, Natalie McCormick: None declared, Hyon Choi Consultant of: Have received consulting fees from LG Pharma, Horizon Therapeutics PLC, Allena Pharmaceuticals, Inc, and Protalix Biotherapeutics outside the submitted work., Grant/research support from: Have received research support from Horizon Therapeutics PLC outside of the submitted work., Diane Lacaille: None declared, J. Antonio Aviña-Zubieta: None declared.