The long-term cancer safety profile of sodium-glucose co-transporter 2 inhibitors (SGLT-2i) remains an area of active investigation in type 2 diabetes mellitus (T2DM). A retrospective cohort study published in Diabetes, Obesity and Metabolism evaluated associations between SGLT-2i initiation and obesity-associated cancers (OAC) using real-world data from the TriNetX US Collaborative Network.

Individuals with T2D initiating SGLT-2i were compared with those initiating dipeptidyl peptidase-4 inhibitors (DPP-4i) using 1:1 propensity score matching to account for key confounders. Individuals with prior cancer or a cancer diagnosed within 6 months after treatment initiation were excluded. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for composite OAC, individual OAC types, and all-cancer outcomes. Analyses were conducted overall, stratified by overweight or obesity status, and across individual SGLT-2i agents.

Initiation of SGLT-2i was not associated with composite OAC compared with DPP-4i in the overall population or within overweight or obesity strata. A lower rate of renal cancer was observed in the overall population (HR 0.78, 95% CI 0.67-0.92) and among individuals with overweight or obesity (HR 0.79, 95% CI 0.66-0.93). A higher rate of thyroid cancer was observed in the overall population (HR 1.37, 95% CI 1.06-1.76). A modest reduction in the all-cancer outcome was observed overall (HR 0.96, 95% CI 0.93-0.99) and among individuals with (HR 0.95, 95% CI 0.91-0.98) and without (HR 0.88, 95% CI 0.78-0.99) overweight or obesity.

These findings indicate no association between SGLT-2i initiation and composite obesity-associated cancers compared with DPP-4i, while modest differences in certain site-specific and overall cancer outcomes were observed.