COA_Karl said:

Metabolic syndrome resolution on cardiovascular risk: I went from meeting 5 of 5 diagnostic criteria to meeting ZERO after 10 months of treatment.

Thank you — that is the clearest version of this I have read, and I have read a lot of them. Taking it to my next appointment.

LindaRN_retired said:

Dr.SportsMedIN said: ...we're creating a generation dependent on cardiovascular risk...

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.

sophie_paris said:

My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.

I want to bring up the cardiovascular angle on cardiovascular risk.

The SELECT trial demonstrated a 20% reduction in MACE with semaglutide 2.4mg[1]. This is practice-changing because the CV benefit appears to be independent of the degree of weight loss — suggesting direct vascular and anti-inflammatory mechanisms.

For cardiovascular risk, this means we need to think beyond the primary outcome and consider the cardiovascular implications. The all-cause mortality reduction (HR 0.81) is the most clinically meaningful signal.

Moderator note: the sourcing question belongs in the vendor section and has been split out.