A Lancet Haematology editorial calls for urgent research as GLP-1 drugs show early signals in malignancy and thrombosis.
Glucagon-like peptide-1 receptor agonists have moved from the periphery of diabetes care to the centre of global medicine – and haematology can no longer afford to watch from the sidelines, according to a new editorial in The Lancet Haematology.
Originally approved by the US Food and Drug Administration in 2005 for type 2 diabetes and later for obesity, GLP-1RAs have transformed cardiometabolic medicine.
But emerging observational data suggest their biological reach may extend into clonal haematopoiesis, thromboinflammatory pathways and the natural history of both malignant and non-malignant blood disorders, the authors wrote.
“Although the exact mechanisms by which GLP-1RAs confer benefits independent of weight loss remain incompletely understood, there is growing evidence of systemic anti-inflammatory effects arising from direct and indirect immune, vascular and neural crosstalk, along with interactions with several cellular signalling pathways that might inhibit proliferation and promote apoptosis,” they wrote.
“Building on these potential mechanisms, last year preliminary data from observational studies evaluating their effects in haematological conditions began to emerge.”
The mechanistic rationale was compelling, they wrote. GLP-1RAs appear to exert systemic anti-inflammatory effects, modulate endothelial function and influence immune–vascular signalling networks.
Experimental data suggest interactions with pathways governing cellular proliferation and apoptosis, central processes in myelodysplasia, myeloproliferation and plasma cell evolution.
Given that chronic inflammation and metabolic dysregulation are increasingly recognised as contributors to clonal expansion and malignant progression, it is biologically plausible that GLP-1 signalling could influence haematological disease risk or behaviour.
Observational analyses over the past year have begun to test this hypothesis. In adults with type 2 diabetes, GLP-1RA exposure has been associated with lower risks of incident myelodysplastic syndromes and myeloproliferative neoplasms compared with metformin or insulin.
Relative to insulin, GLP-1RAs were also associated with reduced development of lymphoid leukaemia, non-Hodgkin lymphoma, monoclonal gammopathy, multiple myeloma and amyloidosis.
While retrospective and subject to residual confounding, these findings were notable in a field where preventive strategies for clonal haematological disorders were virtually non-existent, the authors wrote.
Non-malignant haematology may be equally relevant. GLP-1RA therapy has been associated with lower risks of VTE, pulmonary embolism and deep vein thrombosis compared with dipeptidyl peptidase-4 inhibitors in diabetic populations.
In sickle cell disease, patients receiving GLP-1RAs for other indications demonstrated lower mortality, fewer vaso-occlusive crises, reduced ischaemic stroke and decreased thrombotic events. Given the central role of inflammation, endothelial dysfunction and hypercoagulability in sickle cell disease, these findings merited mechanistic exploration.
“These results are encouraging, but should be interpreted with caution given the retrospective design and reliance on a single data source, which might limit their generalisability and representativeness,” the authors wrote.
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“Validation should involve corroboration from multiple datasets and the conduct of prospective studies and clinical trials. Nevertheless, these findings provide a valuable,
The clinical urgency was heightened by expanding global access to GLP-1 drugs, the authors said.
In December 2025, the World Health Organization issued its first guideline endorsing conditional GLP-1 drug use for obesity, acknowledging obesity as a chronic, relapsing disease requiring long-term therapy.
“Furthermore, a recent meta-analysis suggests that after around 39 weeks of treatment, cessation is followed by weight regain of about 0.4 kg per month, with bodyweight returning to baseline in under 2 years, firing up the debate about short-term versus long-term use,” the authors concluded.
“In this context, the haematological field cannot lag behind: as these blockbuster drugs become more widespread, there is an urgent need for more research into the potential benefits of GLP-1 drugs for haematological conditions and for deeper investigation into their mechanism of action. Rigorous data are essential to inform practice, protect patient safety, and ensure the best patient care.”
