Abstract 4144520: Glucagon-like Peptide-1 Receptor Agonists for the Primary Prevention of Major Adverse Cardiac Events in Drug-naïve Type 2 Diabetes: A Propensity-score Analysis

Background: The effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RA) as a first-line agent for the primary prevention of major adverse cardiac events (MACE) in obese patients with diabetes mellitus (DM) is unknown. Research Question: Does initial treatment with GLP-1 RA in obese drug-naïve patients with type 2 DM prevent future MACE? Aims: To examine the association between GLP-1 RA treatment and the primary prevention of MACE in drug-naïve type 2 DM patients with obesity. Methods: A retrospective propensity score-matched (PSM) analysis was conducted using the TriNetX Global database. We implemented a new-user design, including adult overweight/obese patients with drug-naive type 2 DM between January 1 st , 2019 and May 1 st , 2023. Patients with prior heart failure (HF), myocardial infarction (MI), coronary revascularization, stroke, or cardiac arrest were excluded. We compared those starting GLP-1 RA versus starting non GLP-1 RA. Medication starting window spans from the first diagnosis to 3 months afterwards. Patients with insulin were excluded if they had any emergency or inpatient encounters during this window. The primary outcome was incident MACE, defined as any death, decompensated HF, MI, cardiac arrest, or ventricular tachycardia/fibrillation, within 5 years of initial drug dispense. Secondary outcomes were individual MACE. Gastrointestinal bleeding was set as a falsification endpoint. Results: Of 1,245,340 patients with A1c <10% and 293,072 patients with A1c ≥10%, 7,483 and 1,563 patients started on GLP-1 RA as a single agent and part of a combined approach, respectively. After PSM, baseline covariates were balanced between the two treatment groups and no significant differences were observed in the falsification endpoint by treatment arm (Figure) . Compared with non-GLP-1 RA, with the exception of sodium-glucose cotransporter-2 (SGLT2i), starting a GLP-1 RA first was associated with a significant reduction in MACCE, primarily driven by reductions in decompensated HF (Figure) . Conclusions: Initiation of a GLP-1 RA as the first agent for obese patients with drug-naïve type 2 DM was associated with a significant reduction in MACE compared to all other diabetes medications, with the exception of SGLT2i.