From the other side of the consultation, briefly.

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.

PeptideChemSF said:

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

Lp(a) and cardiovascular risk: a nuance that matters. Unlike most lipid markers, Lp(a) is 90%+ genetically determined and doesn't really change with weight loss or GLP-1 therapy.

My Lp(a) has remained at 52 nmol/L across all time points. If yours is elevated (>50 nmol/L), you need additional risk mitigation strategies regardless of your GLP-1 response. Don't assume your medication is covering all cardiovascular risk factors.

One thing that is still open after PeptideChemSF’s answer:

What would you measure differently if you were starting again?

raj_cambridge said:

Lp(a) and cardiovascular risk: a nuance that matters.

Senior perspective on cardiovascular risk: I'm 66 years old and started this journey skeptically. My cardiologist recommended it after years of failed interventions.

14 months later: down 44 lbs, more mobile, pain reduced, medications simplified. My quality of life has improved dramatically. I wish this existed 20 years ago.

To other older adults hesitating: the SELECT trial proved benefit in our age group. You deserve to feel good in your body regardless of age.

Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful.