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.

Summary

In a nationwide, active-comparator, new-user design with large propensity score–matched cohorts, both DPP4 inhibitors and GLP-1 receptor agonists were associated with higher gallbladder/biliary disease risk than SGLT2 inhibitors, without BMI-based effect modification. Findings are consistent across obese, overweight, and normal-weight categories.

Key Findings

• DPP4 inhibitors vs SGLT2 inhibitors: HR 1.21 (95% CI 1.14–1.28) for gallbladder/biliary disease.
• GLP-1 receptor agonists vs SGLT2 inhibitors: HR 1.27 (95% CI 1.07–1.50).
• No evidence of BMI-based effect modification (p=0.83 and p=0.73 for interaction).

Clinical Implications

In patients at higher baseline risk for gallbladder/biliary diseases, preferential consideration of SGLT2 inhibitors over incretin agents may reduce biliary events. Counsel patients on biliary symptoms and monitor accordingly irrespective of BMI.

Limitations

• Observational claims data subject to residual confounding and potential misclassification.
• Absolute risks and follow-up durations are not detailed in the abstract.

Future Directions

Head-to-head pragmatic trials or high-quality emulations assessing absolute risks, duration-response, and mechanisms of biliary effects with incretin therapies.