Lower risks of new-onset acute pancreatitis and pancreatic cancer in sodium glucose cotransporter 2 (SGLT2) inhibitors compared to dipeptidyl peptidase-4 (DPP4) inhibitors: A propensity score-matched study with competing risk analysis

Background
Dipeptidyl peptidase-4 inhibitors (DPP4I) may be associated with higher risks of acute pancreatitis and pancreatic cancer. This study compared the risks of acute pancreatitis and pancreatic cancer between sodium glucose cotransporter 2 inhibitors (SGLT2I) and DPP4I users.

Methods
This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus on either SGLT2I or DPP4I between January 1st, 2015, and December 31st 2020 in Hong Kong. The primary outcome was new-onset acute pancreatitis and pancreatic cancer. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Univariable and multivariable Cox regressions were applied to identify significant predictors.

Results
This cohort included 31609 Type 2 Diabetes Mellitus patients (median age: 67.4 years old [SD: 12.5]; 53.36% males). 6479 patients (20.49%) used SGLT2I, and 25130 patients (70.50%) used DPP4I. After matching, the rate of acute pancreatitis was significantly lower in SGLT2I users compared to DPP4I users. Multivariable Cox regression showed that SGLT2I use was associated with lower risks of acute pancreatitis (Hazard ratio, HR: 0.11; 95% Confidence interval, CI: 0.02-0.51; P=0.0017) and pancreatic cancer (HR: 0.22; 95% CI: 0.039-0.378; P=0.0003). The results were consistent using competing risk models and different propensity score approaches.

Conclusions
SGLT2I use was associated with lower risks of new-onset acute pancreatitis and pancreatic cancer after propensity score matching and multivariable adjustment, underscoring the need for further evaluation in the randomised controlled trial setting.