chris_chi24 said:Relative and absolute effects need reading together.
Thank you — that is the clearest version of this I have read, and I have read a lot of them. Adding it to my notes with a link back to this thread.
Adding the clinical framing, because it changes how the question reads.
nick_newbie 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.Martinez said:The gap between trial results and real-world results is consistent and it is not fraud.
Pushing back on Dr.Martinez here. I would add the less popular caveat: these trial populations under-represented several groups, older adults and the highest BMI categories among them. The results probably generalise, and "probably" should be stated as an assumption rather than dropped.
Happy to go further on any of that.
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Browse GL Biochemnick_newbie said:SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…
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.
Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful. Tagging this one for the weekly digest.