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.