The association between sodium-glucose cotransporter 2 inhibitor and risk of pancreatic cancer among patients with type 2 diabetes mellitus: A real-world cohort study

Pancreatic cancer (PC) is one of the deadliest cancers, with limited screening options and a high mortality rate. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i), a novel class of antidiabetic agents for type 2 diabetes mellitus (T2DM), have shown various benefits, but their long-term impact on PC risk is unclear. We conducted a real-world analysis using the TriNetX database, which aggregates de-identified electronic medical records from over 147 million patients across 120 health care organizations in 17 countries. We created 2 cohorts from 7,788,779 patients with newly diagnosed T2DM. One cohort received SGLT2-i, while the other received dipeptidyl peptidase 4 inhibitors (DPP4-i) as an active comparator. Patients were matched for demographics, comorbidities, serum hemoglobin A1c levels, and antidiabetic drug use. The primary outcome was the relative risk (RR) of PC over a 10-year follow-up. SGLT2-i use was associated with a significantly lower risk of PC compared to DPP4-i use (RR = 0.67; 95% CI = 0.613–0.731). Sensitivity analyses supported these findings across different follow-up periods: 3 years (RR = 0.805; 95% CI = 0.727–0.892) and 5 years (RR = 0.748; 95% CI = 0.682–0.82). Long-term SGLT2-i use in patients with T2DM was associated with a reduced risk of PC compared to DPP4-i use. These findings highlight the potential protective role of SGLT2-i against PC. Further studies, including randomized controlled trials, are warranted to clarify the causal relationship.