A retrospective cohort study on the comparative safety of glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors on the onset of gallbladder disease in type II diabetes

BACKGROUNDS AND OBJECTIVES: To assess and confirm the risk of gallbladder disease in Type II diabetes (T2D) patients treated with Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA) compared to Dipeptidyl Peptidase-4 Inhibitor (DPP-4I). MATERIALS AND METHODS: This is a retrospective cohort study using administrative claims. Adults who newly received either GLP-1RA or DPP-4I for T2D management were identified between 2016 and 2021. Study cohort included individuals naïve to gallbladder disease or relevant condition on or 6-month prior to the first GLP-1RA or DDP-4I dispensing date (Index). Cumulative incidence of gallbladder disease after the minimal follow-up period of the first 45 days was estimated using the Kaplan-Meier method. A Cox proportional hazard regression model was used to calculate hazard ratios of gallbladder disease for GLP-1RA vs. DPP-4I up to 2 years beyond the initial 45-day exposure. RESULTS: The cohort included 135,197 GLP-1RA and 118,919 DPP-4I patients with minor diabetes complication profiles. Cumulative incidence of gallbladder disease at 1 year was 1.286% (GLP-1RA) vs. 1.054% (DPP-4I); at 2 years, it was 2.181% vs. 2.039%. Adjusting for the baseline characteristics, the respective HR (95% CI) was 1.241 (95% CI, 1.104-1.393) at 1 year and 1.176 (95% CI, 1.061-1.304) at 2 years. CONCLUSION: A moderate but significant increase in the risk of gallbladder disease was confirmed from the real-world population receiving GLP‑1 RA compared with DPP‑4I. This confirmed risk underscores the need for ongoing monitoring and surveillance for gallbladder disease during GLP‑1RA therapy.