My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
Relative versus absolute is the distinction that gets lost: a 20% relative reduction on a high baseline risk is a large absolute benefit, and the same relative figure on a low baseline risk is a small one.
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 have searched first, so if this is covered somewhere point me at it and I will read it.
gary_naperville 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.
FDA_TrackerJim said:I want to bring up the cardiovascular angle on cardiovascular risk.
FDA_TrackerJim said:...cardiovascular risk is just another fad...
I understand the skepticism — we've all seen "miracle" weight loss solutions come and go. But consider what makes GLP-1 agonists different:
- Phase 3 RCTs with thousands of participants (not 20-person pilot studies)
- Published in NEJM, JAMA, Lancet (not press releases)
- Replicated across multiple independent research groups
- Proven cardiovascular and renal benefits beyond weight loss
- Biological mechanism fully characterized at the receptor level
This isn't a fad — it's a new drug class supported by the highest level of clinical evidence. The comparison to past fads is understandable but inappropriate.
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Browse GL Biochemgary_naperville said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
Mine went the same way, slower. I had assumed I was the exception until I read this.
Adding the clinical framing, because it changes how the question reads.
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 57 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.