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Updated: Apr 14, 2026

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Association of SGLT2 inhibitors with hematologic malignancies in type 2 diabetes: a target trial emulation study

Yuan-Tsung Tseng1, Chang-Sung Tsai2, Mita Restinia3

  • 1Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medical Research, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan.

Diabetes Research and Clinical Practice
|April 5, 2026
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) showed a reduced risk of hematologic malignancies, including leukemia and multiple myeloma, compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) in type 2 diabetes patients.

Area of Science:

  • Endocrinology and Oncology
  • Pharmacovigilance
  • Diabetes Mellitus Research

Background:

  • Type 2 diabetes mellitus (T2DM) management involves various drug classes.
  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) are common antidiabetic agents.
  • Understanding the comparative safety profiles of these medications regarding hematologic malignancies is crucial.

Purpose of the Study:

  • To compare the risk of hematologic malignancies between SGLT2i and DPP-4i users with T2DM.
  • To identify specific hematologic malignancy subtypes associated with each drug class.

Main Methods:

  • Retrospective cohort study utilizing the TriNetX US Collaborative Network (2010-2025).
  • Target trial emulation with 1:1 propensity score matching (PSM) for new users of SGLT2i and DPP-4i.
  • Robustness checks included E-values for unmeasured confounding and landmark analyses with outcome controls.

Main Results:

  • In a balanced cohort (243,852 patients/group), SGLT2i use was linked to a lower risk of overall hematologic malignancies versus DPP-4i (aHR 0.90; 95% CI, 0.84-0.95).
  • Subtype analysis indicated reduced risk for leukemia (aHR 0.85; 95% CI, 0.77-0.94) and multiple myeloma (aHR 0.85; 95% CI, 0.75-0.97).
  • No significant association was observed for lymphoma risk (aHR 0.97; 95% CI, 0.89-1.06).

Conclusions:

  • SGLT2i use is associated with a decreased risk of hematologic malignancies compared to DPP-4i in T2DM patients.
  • The protective association is particularly noted for leukemia and multiple myeloma.
  • Further research is recommended to confirm these findings and elucidate underlying mechanisms.
Keywords:
DPP-4 inhibitorsHematologic malignanciesLeukemiaMultiple myelomaSGLT2 inhibitorsType 2 diabetes mellitus

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