Association of GLP1-Receptor Agonists With Risk of Hematologic Malignancies in People With Diabetes

Glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely used for the management of diabetes mellitus and obesity. Despite growing literature on GLP-1RA use and obesity-related cancers, the association between GLP-1RA use and hematologic malignancies are relatively underexplored.

We conducted a retrospective cohort study using the Veterans Affairs (VA) national data, including patients with diabetes initiating GLP-1RA or dipeptidyl peptidase-4 inhibitors (DPP-4i), as active comparators, during years 2006 to 2021. An active comparator, new-user design was used. Propensity score matching was performed using 71 baseline covariates. The primary outcome was an incident diagnosis of Hodgkin lymphoma, non-Hodgkin lymphoma, leukemias, or multiple myeloma.

Among 409,334 eligible patients with diabetes, 100,038 matched pairs were included. In the propensity score-matched cohort, incidence of our outcomes in DPP4i users versus GLP-1RA users were as follows: Hodgkin's lymphoma 36 (0.04%) versus 32 (0.03%) (odds ratio [OR]: 0.89; 95% confidence interval [CI]: 0.55-1.43; P = .63), non-Hodgkin's lymphoma 260 (0.3%) versus 253 (0.3%) (OR: 0.97; 95% CI, 0.82-1.16; P = .76), leukemias 258 (0.3%) versus 248 (0.3%) (OR: 0.96; 95% CI, 0.81-1.14; P = .66), and multiple myeloma 126 (0.1%) versus 115 (0.1%) (OR: 0.91; 95% CI, 0.71-1.18; P = .48), respectively. Findings were consistent across most subgroup analyses by duration of therapy, baseline body mass index, and weight change.

In this large national cohort of veterans with diabetes, GLP-1RA use was not associated with an increased or decreased risk of hematologic malignancies compared to DPP-4i.