Sodium‐Glucose Cotransporter 2 Inhibitors and Cancer Risk in Patients With Type 2 Diabetes Mellitus: An Active Comparator, New‐User Cohort Study

The association between sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2i) and cancer risk in type 2 diabetes mellitus (T2DM) patients remains controversial. This study aimed to investigate whether SGLT‐2i use is associated with a reduced risk of overall or site‐specific cancer. Using the Shenzhen Public Health Data Platform, we emulated a target trial with an active‐comparator, new‐user design. Dipeptidyl peptidase‐4 inhibitors (DPP‐4i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) were used as reference medications. Hazard ratios (HRs) and 95% confidence intervals (CIs) were assessed using overlapping weighting‐based Cox proportional hazards models. The cohort included 134,481 patients when using DPP‐4i as comparator. During a median follow‐up of 1.8 years, 1848 (2.2%) and 1557 (3.0%) cancer cases were identified among SGLT‐2i and DPP‐4i users. After adjusting for confounders, SGLT‐2i was associated with a lower risk of overall cancer compared with DPP‐4i (HR: 0.91; 95% CI: 0.85–0.98). A negative association was observed for site‐specific cancers, including lung (HR: 0.84; 95% CI: 0.72–0.98) and thyroid cancer (HR: 0.76; 95% CI: 0.61–0.96). In the comparison between SGLT‐2i and GLP‐1RA, 3371 (2.58%) cancer cases occurred. After adjustment, no significant difference in overall cancer risk was observed between SGLT‐2i and GLP‐1RA users (HR: 1.03; 95% CI: 0.85–1.25). SGLT‐2i was associated with a reduced risk of lung and thyroid cancers compared with DPP‐4i, while no statistically significant difference was observed relative to GLP‐1RA. These findings provide supportive evidence for the safety of SGLT‐2i regarding carcinogenic risk and suggest its potential role in cancer prevention strategies among T2DM patients.