Beyond weight loss
Semaglutide, known as Ozempic or Wegovy, is widely recognized for improving blood sugar and promoting weight loss. Large trials also show fewer cardiovascular events, but the underlying biology has remained elusive. Experimental work pointed to anti‑inflammatory effects; this study is one of the first in humans to interrogate blood, bone marrow and vascular inflammation together. “There is a lot of public focus on GLP‑1 drugs as weight‑loss medication,” says co-senior author Dr. Nordin Hanssen. “Our work reminds us that these agents were developed for diabetes, and that their cardiovascular benefits may be closely tied to how they modulate inflammation and immune cells in the bone marrow and blood.”
Unique integrated approach
In 16 people with poorly controlled type 2 diabetes, the team collected blood and sternal bone marrow aspirates before and after six months of semaglutide. They combined advanced flow cytometry of monocyte subsets and hematopoietic progenitors with a broad inflammatory marker panel and 68Ga‑DOTATATE PET‑CT scans of bone marrow, spleen and coronary arteries. This integrated “cardio‑hematopoietic” approach allowed the researchers to see how semaglutide‑associated changes in metabolism, immune cells and inflammatory mediators might fit together, rather than looking at a single compartment in isolation.
Nordin Hanssen and Jeffrey Kroon after receiving the Dutch Heart Foundation Dekker Grants
Fewer inflammatory cells
After treatment, the proportion of circulating non‑classical CD16‑positive monocytes, a subset linked to vascular inflammation and plaque erosion, was clearly lower, while total monocyte numbers stayed similar. In bone marrow, imaging showed reduced 68Ga‑DOTATATE uptake, consistent with a less activated myeloid phenotype. At the same time, many inflammatory cytokines and endothelial activation markers in the blood were reduced, including key chemokines and adhesion molecules. “We see a coherent pattern: fewer pro‑inflammatory monocytes, lower bone marrow inflammatory signal, and reduced endothelial activation markers,” says co‑senior author Dr. Jeffrey Kroon. “Taken together, these signals fit with a model in which semaglutide reduces the flux of activated monocytes toward the arterial wall, which could over time lower the risk of plaque erosion and thrombus formation.”
No short‑term plaque effect
Despite the changes in bone marrow and blood, 68Ga‑DOTATATE uptake in coronary arteries did not decrease over six months. This negative primary endpoint, and the small, uncontrolled design, mean the findings are associative and hypothesis‑generating rather than proof of mechanism. The authors emphasize that GLP‑1 receptor agonists should be viewed as complementary to intensive lipid‑lowering therapy, not a substitute. “Our data do not prove causality, and larger controlled trials are needed,” Hanssen cautions. “But this is a unique, integrated snapshot of the bone marrow, immune system and endothelium under GLP‑1 therapy in humans. It helps us think more precisely about how these drugs might protect the heart and vessels.”
The findings were published in European Heart Journal. The study was supported by two Dekker grants from the Dutch Heart Foundation for senior authors Nordin Hanssen and Jeffrey Kroon.