Is Semaglutide Anti-inflammatory?

LYON, FRANCE — The anti-weight problems drug semaglutide is said with significant reductions within the inflammatory marker excessive-sensitivity C-reactive protein (CRP), even in sufferers who attain now not lose substantial quantities of weight with the drug, in accordance to data from the SELECT clinical trial.

The analysis, presented at the European Atherosclerosis Society 2024, fervent over 17,600 sufferers with chubby or weight problems and had established cardiovascular disease but now not diabetes.

Those given semaglutide experienced a 38% cut value in excessive-sensitivity CRP ranges in comparison with placebo irrespective of baseline body mass index, statin exercise, cholesterol ranges, and diverse measures.

“Weight reduction changed into related with bigger excessive-sensitivity CRP cut value in both therapy groups,” stated see presenter Jorge Plutzky, MD, director of Preventive Cardiology at Brigham and Girls folks’s Hospital, Boston, Massachusetts, but “with elevated excessive-sensitivity CRP reductions in these receiving semaglutide.”

The drug furthermore “enormously diminished excessive-sensitivity CRP early,” he stated, “forward of critical weight reduction and in of us that failed to lose significant quantities of weight.” The reductions reached roughly 12% at 4 weeks and round 20% at 8 weeks, when the weight reduction “changed into restful reasonably modest,” at 2% and 3% of body weight, respectively. Even among sufferers who completed weight lack of now not as a lot as 2% body weight, semaglutide changed into related with a cut value in excessive-sensitivity CRP ranges.

Within the SELECT trial, semaglutide furthermore resulted in a consistent cut value of round 20% vs placebo in critical negative cardiovascular events equivalent to cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke.

However Naveed Sattar, MD, PhD, professor of cardiometabolic medication at the University of Glasgow, Scotland, United Kingdom, stated in an interview that body weight “is potentially the critical driver” of CRP ranges within the inhabitants, accounting for between 20% and 30% of the variation.

Sattar, who changed into now not captivated with the see, stated that because medication like semaglutide lower weight but furthermore bear anti-inflammatory outcomes, the query becomes: “Could well perhaps perhaps the anti-inflammatory outcomes be fragment of the mechanisms by which these medication have an effect on the trouble of critical negative cardiovascular events?”

Reducing Cardiovascular Events

Essentially the most approved analysis, nonetheless, can’t acknowledge the query, he stated. “All it tells us is about associations.”

“What we attain know is semaglutide, predominantly by lowering weight, is lowering CRP ranges and equally, we know that after you fall pounds, you toughen blood stress, you toughen lipids, and also you lower the trouble of diabetes,” he stated.

Sattar furthermore took location with the researchers’ conclusion that the excessive-sensitivity CRP reductions viewed in SELECT happened forward of critical weight reduction because the “sample of CRP cut value and weight cut value is practically identical.”

Sattar furthermore pointed out in a most approved editorial that the drug looks to bear a straight away attain on blood vessels and the guts, that will presumably well also consequence in enhancements in systemic inflammation. Consequently, he stated, any assertion that semaglutide is that in fact anti-inflammatory is, at this stage, “hypothesis.”

Plutzky stated that “systemic, power inflammation is implicated as a doable mechanism and therapeutic target in atherosclerosis and critical negative cardiovascular events, to boot to weight problems,” and excessive-sensitivity CRP ranges are an “established biomarker of inflammation and had been shown to predict cardiovascular trouble.”

On the more than a few hand, the relationship between excessive-sensitivity CRP, responses to glucagon-like peptide 1 receptor agonists like semaglutide, and cardiovascular outcomes in weight problems “remains incompletely understood,” stated Plutzky.