Introduction: Glucagon-like peptide-1 (GLP-1) agonists are a staple in the treatment of type 2 diabetes mellitus and obesity. Since obesity is implicated in the pathogenesis of various malignancies, the impact of weight loss medications on cancer risk needs to be defined. GLP-1 agonists elevate the risk of medullary thyroid cancer but are also associated with reduced risk of obesity-related neoplasms including colorectal and pancreatic cancers. Though studies have previously linked obesity to multiple myeloma and leukemias, the role of GLP-1 agonists in modifying this risk is unclear.

Methods: We analyzed risk of four hematologic malignancies in de-identified electronic health record data from a multi-institutional database using a time-dependent cox proportional hazard model. We compared individuals with type 2 diabetes mellitus using GLP-1 agonists, SGLT2 inhibitors, or neither. Information from 544,016 individuals was included and weighted for demographics and risk factors for microvascular and macrovascular complications. Risk of mortality associated with medication use was also assessed in individuals with type 2 diabetes mellitus and the malignancies of interest.

Results: At baseline, GLP-1 agonist users were younger, had higher BMI, and less chronic kidney disease, ischemic heart disease, and heart failure than non-users. SGLT2 inhibitor users had more ischemic heart disease and heart failure than non-users. After weighting, use of either drug type did not alter risk of acute myeloid leukemia (GLP-1 HR 0.81, p=0.354; SGLT2 HR 1.22, p=0.298), chronic myeloid leukemia (GLP-1 HR 1.06, p=0.857; SGLT2 HR 1.23, p=0.428), or myelodysplastic syndrome (GLP-1 HR 0.98, p=0.891; SGLT2 HR 1.0, p=0.996). However, in contrast to SGLT2 inhibitors, GLP-1 agonist use was associated with lower risk of multiple myeloma (GLP-1 HR 0.64, p = 0.01, SGLT2 HR 1.12, p = 0.358). This effect was also true for patients with HbA1c > 8% or BMI > 30. Further, we observe an increased risk of mortality associated with SGLT2 inhibitor use in diabetics with acute myeloid leukemia (HR 2.00, p = 0.006) and multiple myeloma (HR 2.27, p < 0.001), independent of the covariate of heart failure.

Conclusions: GLP-1 agonist use in type 2 diabetes is associated with a reduced risk of multiple myeloma and is not associated with mortality risk in diabetics with the studied hematologic malignancies. Further investigation into potential risks of SGLT2 inhibitors in patients with multiple myeloma and acute myeloid leukemia is warranted.

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2025
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