GLP-1 RA Use Linked to Lower Hematologic Cancer Risk in T2D Patients: JAMA
According to a study published in JAMA Network Open, among patients with type 2 diabetes (T2D), the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA) was associated with a reduced risk of developing hematologic cancers compared to insulin and metformin use.
Type 2 diabetes (T2D) and obesity are independent risk factors for various cancers, including hematologic cancers. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained attention for their role in glycemic control, weight loss, and immune modulation. While they are associated with lower risks of solid tumors, their impact on hematologic cancers remains unclear.
This study aims to compare hematologic cancer risks in T2D patients treated with GLP-1RAs versus metformin and insulin. Using data from the TriNetX electronic health record platform, a retrospective cohort study was conducted, including 1,601,334 T2D patients prescribed GLP-1RAs, metformin, or insulin between 2005 and 2023. Patients were excluded if they had prior hematologic cancer diagnoses or used antidiabetic medications before their T2D diagnosis. The primary outcome was the first diagnosis of hematologic cancer within 15 years.
Propensity score matching was performed to control for demographic and clinical variables. After matching, 47,716 patients were included in the GLP-1RA–insulin comparison and 50,590 in the GLP-1RA–metformin comparison. GLP-1RA use was associated with a significantly lower risk of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) compared to metformin. Compared to insulin, GLP-1RAs significantly reduced risks of multiple hematologic cancers, including myeloid and lymphoid leukemia, non-Hodgkin lymphoma, multiple myeloma, and amyloidosis.
The study suggests that GLP-1RAs may lower hematologic cancer risk, potentially due to weight loss and immunomodulatory effects. The protective effect appears independent of glycemic control and may be linked to reduced proinflammatory cytokines. While metformin has potential cancer-protective properties, its effects were less pronounced than GLP-1RAs. Study limitations include reliance on medical codes, residual confounding, and lack of age stratification. Further research is needed to explore the biological mechanisms underlying GLP-1RA-associated cancer risk reduction.
Reference:
Ashruf OS, Hundal J, Mushtaq A, Kaelber DC, Anwer F, Singh A. Hematologic Cancers Among Patients With Type 2 Diabetes Prescribed GLP-1 Receptor Agonists. JAMA Netw Open. 2025;8(3):e250802. doi:10.1001/jamanetworkopen.2025.0802
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