The Risk of Acute Pancreatitis and Biliary Events After Initiation of Incretin-Based Medications In Patients with Type 2 Diabetes

<p dir="ltr">Objective: Patients with type 2 diabetes (T2D) are at increased risk of acute pancreatitis (AP) and biliary events. Evidence remains mixed regarding the association between incretin-based therapies – glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP4i) – and these outcomes. We examined the association between incretin medication use and risk of incident AP or biliary disease in patients with T2D.</p><p dir="ltr">Research Design and Methods: Using Medicare FFS and 2 U.S. commercial claims databases (2014-2021), we identified three pairwise cohorts of propensity-score (PS) fine-stratification-weighted patients aged ≥18 years (≥65 years in Medicare FFS) with T2D without prior AP or biliary disease who initiated GLP-1RA vs sodium-glucose cotransporter-2 inhibitors (SGLT2i), DPP4i vs SGLT2i, or GLP-1RA vs DPP4i. PS was estimated using 92 covariates. Weighted hazard ratios (HRs) with 95% CIs for hospitalization for AP and biliary events were estimated using Cox models.</p><p dir="ltr">Results: Each cohort included over 1.2 million patients. After weighting, GLP-1RA and DPP4i initiators had similar risk of AP vs. SGLT2i initiators (HR[95%CI], 1.01[0.90-1.13] and 1.00[0.85-1.15], respectively). However, both GLP-1RA and DPP4i initiators showed a modestly increased risk of biliary disease vs. SGLT2i (HR, 1.15[1.05-1.26] and 1.22[1.03-1.46], respectively), equivalent to <1 additional event per 1,000 person-years. There was no difference in risk of AP (HR, 1.08[0.95–1.22]) or biliary disease (HR, 0.95[0.86–1.04]) between GLP-1RA and DPP4i.</p><p dir="ltr">Conclusions: In patients with T2D, GLP-1RA or DPP4i were associated with a small increase in risk of biliary disease – but not AP – compared with SGLT2i.</p>