My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
So the question, as narrowly as I can put it: how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.
Tell me what I have not thought of.
InsuranceTom 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.
[1] Lincoff AM, et al. N Engl J Med. 2023;389(24):2221-2232.
Dr.GastroMayo said:I want to bring up the cardiovascular angle on cardiovascular risk.
Dizziness and cardiovascular risk: I was lightheaded for the first 2 weeks. Root cause was a combination of reduced caloric intake and mild dehydration.
Fix: minimum 80-100oz water daily, don't skip meals even if you're not hungry (eat small protein-rich snacks), and stand up slowly from sitting/lying positions. Also check your blood pressure — GLP-1-induced weight loss can make BP meds too strong, requiring dose reduction.
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Browse GL BiochemInsuranceTom said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
Second this.
Adding the clinical framing, because it changes how the question reads.
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.