Association Between <scp>SGLT2</scp> Inhibitors and <scp>DPP</scp> ‐4 Inhibitors Use and Risk of Acute Pancreatitis: Findings From Nationwide Case‐Based Analyses

AIMS: The Korean national health insurance claims database was utilised to investigate the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) or dipeptidyl peptidase-4 inhibitors (DPP-4i) and the risk of acute pancreatitis (AP). MATERIALS AND METHODS: Patients with type 2 diabetes mellitus prescribed DPP-4i or SGLT2i at least once between January, 2018 and December, 2020 were included. AP was defined by ICD-10 code K85.x in either the principal or first additional diagnosis during hospital admission. Prescription status of the anti-diabetic medications was compared between the hazard period (30 days before AP) and the preceding control periods of the same length with 120 days of washout periods, using conditional logistic regression adjusted for other anti-diabetic and AP-related medications. To account for increasing exposure trends, the case-case-time-control design was applied to minimise bias. A nested case-control study was conducted to ensure the robustness of the controls defined within the current type 2 diabetes mellitus cohort. RESULTS: A total of 7219 AP cases were included. In the case-case-time-control analysis, the risk between the AP and SGLT2i (adjusted odds ratio, 95% confidence interval 0.84, 0.52-1.35) and DPP-4i (aOR 0.93, 95% CI 0.75-1.15) was negligible. The nested case-control study further supported these findings, as the use of SGLT2i (aOR 1.05, 95% CI 0.91-1.21) or DPP-4i (aOR 1.01, 95% CI 0.94-1.09) within a 30-day time window was not associated with the risk of AP. CONCLUSIONS: Neither SGLT2i nor DPP-4i is associated with an increased risk of AP in patients with type 2 diabetes mellitus after accounting for prescription trends.