A surprise link between inflammation, clonal blood stem cells, and a blockbuster drug opens new questions in blood cancer research.

In recent years, glucagon-like peptide-1 receptor agonists (GLP-1RAs) — the class of drugs that includes Ozempic, Wegovy, and others — transformed care for type 2 diabetes and obesity.

Now, new research from Cleveland Clinic physician-scientist Dr. Abhay Singh suggests these same drugs may do more than regulate metabolism — they may influence the risk of rare, inflammation-driven blood cancers like myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDSs).

What GLP-1 drugs are and what else they might do

GLP-1 receptor agonists (GLP-1RAs) have seen a meteoric rise in popularity since the first drug in this class, exenatide, was approved by the FDA in 2005. These therapies are now widely used for both type 2 diabetes and weight management. By activating GLP-1 receptors found in the intestine, brain, heart, and other tissues, GLP-1RAs can:

• help regulate blood sugar

• protect the cells responsible for producing insulin

• slow stomach emptying

• promote feelings of fullness

Caption: GLP-1RAs have direct and indirect effects on a diverse group of tissues and cell types, increasing or decreasing their activity. Originally published in Frontiers in Endocrinology, Zhao et al., 2021 

Although GLP-1RAs act on multiple tissues throughout the body, the exact mechanisms behind their wide-ranging effects remain unclear. One especially intriguing outcome, however, has caught researchers’ attention: “They decrease inflammation by unknown mechanisms,” Dr. Singh. says, then laughs. “If anyone would say they know the mechanism, they would be making a lot of things up!” Singh and others in the field have seen patterns worth pursuing. “Your weight goes down, the chronic state of inflammation or unchecked inflammation improves.” 

That matters, especially in cancers like MPNs and MDSs, where inflammation fuels the growth of harmful clones of blood-forming cells. Singh’s new study sets out to explore whether patients on GLP-1RAs might experience lower rates of these inflammation-linked blood cancers.