My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
The question I want answered is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
If the honest answer is that nobody knows, that is a useful answer and I would rather have it.
SaraMom3 said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
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.
[1] Hogan AE, et al. Diabetologia. 2014;57(4):781-784.
Dr.ObesityMed said:Anti-inflammatory mechanisms of GLP-1 agonists and cardiovascular risk: beyond weight loss, GLP-1R activation directly suppresses NF-κB signaling,…
Continuous metabolic monitoring dashboard for cardiovascular risk — I track everything in a spreadsheet and here's the month-over-month trend for my key markers:
Weight: consistent downtrend, -2.4 lbs/week average
Fasting glucose (finger stick): stable at 87 mg/dL
Blood pressure (home): 119/73 average
Resting heart rate: 67 bpm (down from 83)
Waist circumference: down 17 inches total
The resting heart rate improvement correlates with cardiovascular fitness gains. Everything is moving in the right direction.
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Browse GL BiochemSaraMom3 said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
Can confirm. Same sequence, different timescale. The detail I would add is minor and it is already implied above.
Clinical perspective, offered as context rather than as advice.
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.
[1] Lincoff AM, et al. N Engl J Med. 2023;389(24):2221-2232.