Dr.RaviCardio said:
SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…
Anti-inflammatory mechanisms of GLP-1 agonists and cardiovascular risk: beyond weight loss, GLP-1R activation directly suppresses NF-κB signaling, reduces NLRP3 inflammasome activation, and decreases monocyte/macrophage adhesion to endothelium[1].
Clinical correlates: hsCRP reduction of 30-60% (consistently seen across trials), reduced carotid intima-media thickness, and decreased coronary plaque inflammation on PET imaging.
These anti-inflammatory effects likely contribute to the cardiovascular benefit seen in SELECT — and may explain benefits beyond what weight loss alone would predict.
References:
[1] Hogan AE, et al. Diabetologia. 2014;57(4):781-784.