Tatewaki_2026_Diabetes.Obes.Metab__

AIMS: We investigated whether dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with a higher risk of acute pancreatitis compared with sodium-glucose cotransporter 2 inhibitor (SGLT2i) use in antidiabetic medication-naive individuals. MATERIALS AND METHODS: In this target trial emulation study of medication-naive individuals with diabetes from a Japanese claims database from April 2014 to August 2023, the risk of acute pancreatitis was compared between new users of DPP-4is and new users of SGLT2is. After adjusting for confounders using propensity score-based overlap weighting, we used Cox proportional hazards models for hospitalization due to acute pancreatitis to estimate the hazard ratio (HR) and 95% confidence interval (CI) within the groups in both the intention-to-treat and per-protocol analyses. We also calculated incidence rate differences (IRDs) per 1000 person-years. RESULTS: This study included 26 133 DPP4-i and 6497 SGLT2i users. DPP-4i use was not significantly associated with a higher risk of acute pancreatitis compared with SGLT2i use; the adjusted HRs were 0.97 (95% CI, 0.51-1.83) and 1.11 (95% CI, 0.54-2.27), with IRDs of -0.05 (95% CI, -0.97 to 0.87) and 0.15 (95% CI, -0.86 to 1.15) per 1000 person-years in the intention-to-treat and per-protocol analyses, respectively. CONCLUSIONS: Although small differences cannot be excluded given the width of the CIs for the estimated HRs, the small IRDs observed suggest that any potential difference, if present, is likely to be clinically modest. Therefore, acute pancreatitis risk may not be a major determinant when selecting initial therapy.