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.
I would rather have one careful answer than five confident ones.
tammy_FL 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.
amsterdam_pete said:I want to bring up the cardiovascular angle on cardiovascular risk.
NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).
From SELECT trial: MACE at 39 months — 6.5% semaglutide vs 8.0% placebo. ARR = 1.5%. NNT = 67 over 3.3 years.
Compare to established therapies:
| Intervention | NNT | Timeframe |
|---|---|---|
| Semaglutide (MACE) | 67 | 3.3 years |
| Statins primary prevention (MI) | ~100 | 5 years |
| Aspirin secondary prevention | ~77 | 2 years |
These NNTs are clinically meaningful and comparable to accepted cardiovascular interventions.
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Browse GL Biochemtammy_FL 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.
Adding the clinical framing, because it changes how the question reads.
Dizziness and cardiovascular risk: I was lightheaded for the first 3 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.