Dr.RaviCardio 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.
Following on from jim_asheville — and this may be the naive question:
How would you tell the difference between that and the alternative explanation?
BiostatsBrad said:NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).
Cardiac biomarkers and cardiovascular risk: my cardiologist ordered advanced cardiac labs given my family history. Results were encouraging:
- NT-proBNP: 61 pg/mL (normal, cardiac function preserved)
- Lp(a): 61 nmol/L (genetic, unchanged — expected)
- ApoB: dropped from 151 to 86 mg/dL (excellent response)
- Coronary calcium score: 0 (unchanged from baseline — reassuring)
The ApoB reduction is particularly meaningful — it's considered the best single predictor of cardiovascular risk. GLP-1 therapy seems to improve this consistently.
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Browse GL BiochemBiostatsBrad said:NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).
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.
LindaRN_retired said:Cardiac biomarkers and cardiovascular risk: my cardiologist ordered advanced cardiac labs given my family history.
6 month update on cardiovascular risk: down 38 lbs, off blood pressure meds, A1C normalized. Genuinely life-changing.