Editor: Deborah Sesok-Pizzini, MD, MBA, adjunct professor, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Hematologic cancers among patients with type 2 diabetes prescribed GLP-1 receptor agonists
May 2025—Independent risk factors for many cancers include health conditions such as type 2 diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLA-1RAs) are an effective treatment for these chronic conditions and provide glycemic control, weight reduction, and immunomodulation. In a recent study (Wang L, et al. JAMA Netw Open. Published online July 5, 2024. doi:10.1001/jamanetworkopen.2024.21305), GLP-1RAs were associated with lower cancer risk in solid tumor cancers. However, the relationship between GLP-1RAs and hematological cancers has not been explored. Therefore, the authors conducted a study to compare the risk of hematological cancers in patients with type 2 diabetes treated with GLP-1RAs to that of patients with type 2 diabetes treated with metformin or insulin. The primary outcome was a first diagnosis of a hematological cancer within 15 years of an antidiabetic drug being prescribed. The retrospective cohort study used TriNetX, a repository of aggregated electronic health record data of medical encounters for approximately 25 percent of the U.S. population. The platform includes medical information from various age groups, racial and ethnic backgrounds, income levels, and insurance types. The study cohort comprised patients with type 2 diabetes who were prescribed GLP-1RAs, insulin, or metformin between April 30, 2005 and Oct. 31, 2023. The study excluded patients who received any antidiabetic medication before a diagnosis of type 2 diabetes and those with a prior history of hematological cancers. The investigators performed two analyses—the first comparing patients receiving only GLP-1RA with those receiving only metformin and a second comparing patients receiving only GLP-1RA with those receiving only insulin. The study groups were independently matched using a 1:1 nearest neighbor greedy matching algorithm for demographic and other variables. The latter included diabetic complications, hemoglobin A1C, genetic susceptibility, cancer screenings, radiation, cytotoxic agents, antidiabetic agents, intensive care unit admissions, and adverse social determinants. Statistical analysis was performed using Cox proportional hazard and Kaplan-Meier survival analyses with censuring applied. The statistical significance calculations were two sided and paired. The study group included 1,601,334 patients with type 2 diabetes who were receiving any of the three therapeutic regimens—GLP-1RA (51,617), metformin (611,115), or insulin (938,602). After matching, there were 47,716 patients in the GLP-1RA–insulin analysis and 50,590 in the GLP-1RA–metformin analysis. Compared with metformin, GLP-1RA was associated with a statistically significantly lower risk of myelodysplastic syndromes (MDSs; hazard ratio [HR], 0.61; 95 percent confidence interval [CI], 0.42–0.89) and myeloproliferative neoplasms (MPNs; HR, 0.67; 95 percent CI, 0.52–0.87). There were no significant differences in risk of any other hematological cancers. When compared with insulin, GLP-1RA use resulted in a significantly lower risk of myeloid leukemia (HR, 0.39; 95 percent CI, 0.25–0.60), lymphoid leukemia (HR, 0.45; 95 percent CI, 0.30–0.68), non-Hodgkin lymphoma (HR, 0.42; 95 percent CI, 0.30–0.58), MDS (HR, 0.19; 95 percent CI, 0.11–0.35), MPN (HR, 0.50; 95 percent CI, 0.41–0.61), monoclonal gammopathy (HR, 0.68; 95 percent CI, 0.52–0.88), multiple myeloma (HR, 0.49; 95 percent CI, 0.31–0.76), and amyloidosis (HR, 0.52; 95 percent CI, 0.27–0.98). Overall, GLP-1RA use was associated with a 54 percent lower risk of hematological cancers than insulin treatment. The study findings suggest that GLP-1RAs are associated with a reduced risk of patients with type 2 diabetes developing many hematological cancers, particularly MDS and MPN. The authors propose that this reduced risk may be due to weight loss or the immunomodulatory properties of GLP-1RAs, or both. Of importance, the associations appear to be independent of glycemic control. This may be due to the reduction in proinflammatory cytokines involved in hematopoiesis dysregulation and the development of MDS and MPN. The authors concluded that use of GLP-1RAs may be a promising strategy for reducing the risk of hematological cancers. However, additional studies are needed to understand the pathways and biological mechanisms of GLP-1RAs in cancer prevention.
Ashruf OS, Hundal J, Mushtaq A, et al. Hematologic cancers among patient with type 2 diabetes prescribed GLP-1 receptor agonists. JAMA Netw Open. 2025. doi:10.1001/jamanetworkopen.2025.0802
Correspondence: Dr. Abhay Singh at singha21@ccf.org