Incretin-based drugs and the risk of gallbladder or biliary tract diseases among patients with type 2 diabetes across categories of body mass index: a nationwide cohort study

Background: Despite emerging evidence of gallbladder or biliary tract diseases (GBD) risk regarding incretin-based drugs, population-specific safety profile considering obesity is lacking. We aimed to assess whether stratification by body mass index (BMI) modifies the measures of association between incretin-based drugs and the risk of GBD. Methods: We conducted an active-comparator, new-user cohort study using a nationwide claims data (2013–2022) of Korea. We included type 2 diabetes (T2D) patients stratified by Asian BMI categories: Normal, 18.5 to <23 kg/m²; Overweight, 23 to <25 kg/m²; Obese, ≥25 kg/m². The primary outcome was a composite of GBD, including cholelithiasis, cholecystitis, obstruction of the gallbladder or bile duct, cholangitis, and cholecystectomy. We used 1:1 propensity score (PS) matching and estimated hazard ratios (HR) with 95% confidence intervals (CI) using Cox models. Findings: New users of DPP4i and SGLT2i were 1:1 PS matched (n = 251,420 pairs; 186,697 obese, 39,974 overweight, and 24,749 normal weight pairs). The overall HR for the risk of GBD with DPP4i vs. SGLT2i was 1.21 (95% CI 1.14–1.28), with no effect modification by BMI (p-value: 0.83). For the second cohort, new users of GLP1RA and SGLT2i were 1:1 PS matched (n = 45,443 pairs; 28,011 obese, 8948 overweight, and 8484 normal weight pairs). The overall HR for the risk of GBD with GLP1RA vs. SGLT2i was 1.27 (1.07–1.50), with no effect modification by BMI (p-value: 0.73). Interpretation: The increased risks of GBD were presented in both cohorts with no evidence of effect heterogeneity by BMI. Funding: Ministry of Food and Drug Safety, Health Fellowship Foundation.