Glucagon-Like Peptide-1 (GLP-1)-Based Therapies and Hematological Malignancies: A Narrative Review of Current and...

Initially introduced for the treatment of type 2 diabetes mellitus (T2DM), glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, have become integral to the management of both diabetes and obesity, with their therapeutic indications now extending to cardiovascular and renal diseases. As prescribing has surged, so too has interest in the oncologic implications of these agents. While the relationship between GLP-1-based therapies and solid tumors has been increasingly studied, their association with hematological malignancies, including leukemia, lymphoma, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and plasma cell dyscrasias, has only recently attracted dedicated investigation. This narrative review synthesizes the current preclinical, epidemiological, and clinical evidence linking GLP-1-based therapies to hematological malignancy risk, incidence, and outcomes. Emerging data from large retrospective cohort studies, findings from randomized controlled trial (RCT) network meta-analyses and observational pharmacoepidemiologic studies conducted in real-world settings suggest a predominantly protective association, though agent-specific heterogeneity exists. Putative mechanisms, including immunomodulation, inhibition of nuclear factor kappa B (NF-κB)-mediated inflammatory signaling, modulation of the bone marrow microenvironment, and reduction of obesity-mediated hematopoietic dysregulation, are discussed. Limitations of the existing evidence base, safety considerations during active cancer therapy, and directions for future prospective investigation are also addressed.