Longevity
Semaglutide linked to fewer inflammatory blood cells in small T2D study
By Life and Health Today Staff, . Life and Health Today.
A study published in the European Heart Journal found that semaglutide, the active ingredient in Ozempic and Wegovy, was associated with a significant reduction in circulating inflammatory immune cells called CD16+ monocytes in people with type 2 diabetes. The reduction was 18.8 percent after six months of treatment, according to the study.
Monocytes are white blood cells that patrol the bloodstream and can drive inflammation when they accumulate in artery walls. CD16+ monocytes are a subset considered particularly pro-inflammatory and have been linked to cardiovascular disease risk. The study measured whether semaglutide, a glucagon-like peptide-1 receptor agonist (a class of drug that mimics a gut hormone to regulate blood sugar and appetite), might be shifting these cells out of circulation and back into the bone marrow.
The researchers enrolled 16 adults with type 2 diabetes, average age 63.2 years, and collected blood samples and, in 14 of the 16 participants, bone marrow samples at the start of the study and again after six months on semaglutide at doses up to 2.0 mg weekly. They also used a specialized imaging scan called gallium-68-labelled DOTA-(Tyr3)-octreotate positron emission tomography-computed tomography, which can detect inflammatory activity in tissues, to look at the bone marrow, spleen, and coronary arteries.
After six months, the participants showed reductions in HbA1c (a measure of average blood sugar over roughly three months) of 21.1 mmol/mol, weight loss of 6.7 kg, and a drop in high-sensitivity C-reactive protein, a blood marker of systemic inflammation, of 1.0 mg/L. The imaging showed a 17.5 percent reduction in inflammatory activity in the bone marrow. Levels of several proteins involved in inflammation and immune cell trafficking also fell, including interleukin-1 receptor antagonist, leptin, E-selectin, and intercellular adhesion molecule-1.
The part that complicates the picture: the imaging showed no reduction in inflammatory macrophages inside the coronary arteries themselves. Macrophages are immune cells that accumulate in artery plaques and are a direct driver of heart attack risk. The bone marrow and blood findings did not translate, at least over six months, into a measurable change at the site that matters most for cardiovascular events.
The researchers described the bone marrow retention of monocytes as correlating with weight loss, which raises a question the study cannot answer: how much of what was observed is semaglutide acting on the immune system directly, and how much is the downstream effect of losing weight and lowering blood sugar? Those two things happened simultaneously, and the study was not designed to separate them.
GLP-1 receptor agonists have already been shown in large randomized trials to reduce cardiovascular events in people with type 2 diabetes. What this study was trying to do is understand one possible biological pathway behind that benefit. The authors describe the cardiovascular-haematopoietic axis, meaning the relationship between heart disease risk and the bone marrow's production of immune cells, as a potential mediator of that cardioprotection.
What this study does not show is that semaglutide reduces cardiovascular events through this mechanism, or that the monocyte changes observed in 16 people will hold up in a larger, more diverse population. Sixteen participants is a very small number. The study had no control group receiving a placebo, which means there is no way to rule out that the changes observed were due to weight loss, improved blood sugar, or other factors rather than semaglutide specifically.
The open question is whether a larger, controlled trial that separates the drug's direct immunological effects from its metabolic effects would find the same bone marrow signal, and whether that signal would eventually show up in the coronary arteries where it would need to be to explain the cardiovascular benefit already documented in trials. That work has not been done yet.