BACKGROUND Glucagon-like peptide-1 receptor agonist (GLP1-RA) is a promising therapy for heart and kidney health in type 2 diabetes mellitus (T2DM). However, information on its GI benefits is limited. This study aimed to investigate the gastrointestinal (GI) outcomes of GLP1-RA use in patients with T2DM. MATERIAL AND METHODS This retrospective cohort study utilized the TriNetX Dataset with a new-user and active-comparator design. The study included 2 304 761 adult patients diagnosed with T2DM and an estimated glomerular filtration rate of ≥60 mL/min/1.73 m² from January 2019 to December 2022. To establish cohorts, we designated users of dipeptidyl peptidase-4 inhibitors (DPP4i) as the control group. Two cohorts were formed for analysis after propensity score matching by baseline characteristics, each comprising 127 216 patients - one using GLP1-RA and the other DPP4i. Cox proportional hazards regression models were used to evaluate GI outcomes over 4 years between groups. RESULTS After matching, the average age of the population was about 60 years, with approximately 55% male and 63% identifying as White people. GLP1-RA users demonstrated a lower risk of acute pancreatitis (hazard ratio [HR]: 0.90, 95% confidence interval [CI]: 0.83-0.97), liver failure (HR: 0.81, 95% CI: 0.75-0.88), peritonitis (HR: 0.85, 95% CI: 0.76-0.94), peptic ulcer (HR: 0.89, 95% CI: 0.84-0.94), and GI bleeding (HR: 0.95, 95% CI: 0.92-0.98) compared to DPP4i users, indicating significant GI-protective effects. Furthermore, the GI advantages of GLP14A over DPP4i were consistently observed across various propensity score matching models. CONCLUSIONS GLP1-RA treatment in T2DM has some GI advantages compared to DPP4, which should be considered when personalizing T2DM treatment.
