Differences in long-term safety profiles across glucose-lowering therapies remain an important consideration in type 2 diabetes (T2D) management. A retrospective cohort study published in Diabetes Research and Clinical Practice evaluated whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with a different risk of hematologic malignancies compared with dipeptidyl peptidase-4 inhibitors (DPP-4i).

The analysis used the TriNetX US Collaborative Network (2010-2025) and applied a target trial emulation framework. New users of SGLT2i and DPP-4i were balanced using 1:1 propensity score matching (PSM), resulting in 243,852 patients in each group. Additional analyses included E-values to assess potential unmeasured confounding, along with landmark analyses and outcome controls to evaluate robustness.

SGLT2i use was associated with a lower observed risk of incident hematologic malignancies compared with DPP-4i (adjusted hazard ratio [aHR] 0.90; 95% confidence interval [CI], 0.84-0.95). Subtype analyses showed lower observed risks for leukemia (aHR 0.85; 95% CI, 0.77-0.94) and multiple myeloma (aHR 0.85; 95% CI, 0.75-0.97), while lymphoma risk showed no significant difference (aHR 0.97; 95% CI, 0.89–1.06).

These findings indicate an association between SGLT2i use and lower observed risk of certain hematologic malignancies compared with DPP-4i. Further studies are required to clarify causality and underlying mechanisms.