TirzTom said:Dizziness and cardiovascular risk: I was lightheaded for the first 2 weeks.
This is where I part company with the consensus forming above. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.
LibrarianMeg said:My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.
LibrarianMeg said:...we don't know the long-term effects of cardiovascular risk...
This is a fair point, and I think intellectual honesty requires acknowledging it. GLP-1 agonists in their current form have ~8-10 years of human exposure data. That's not nothing, but it's not 30+ years either.
However: the risk-benefit calculation should also consider the KNOWN long-term effects of untreated obesity — diabetes, cardiovascular disease, cancer, joint destruction, reduced lifespan by 5-10 years.
Uncertainty about GLP-1 long-term safety vs certainty about obesity consequences. The calculus seems clear to me, but reasonable people can disagree.
Dr.NateNeph said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
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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Dr.PulmRoch said:NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).
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 60 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.