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:

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.

BiostatsBrad 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.

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.