Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using it.
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 in major adverse cardiovascular events in people with established cardiovascular disease and overweight or obesity, without diabetes. The effect appeared earlier than the weight-loss curve can comfortably explain, which is the basis for arguing that some of the benefit is direct — anti-inflammatory and vascular — rather than purely a consequence of weight.
Where I think it is weakest: the follow-up is short relative to how long people actually take these drugs, so durability is an assumption here rather than a finding.
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. Tell me what I have not thought of.
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
DeniseRN_TPA 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…
CRP reduction on cardiovascular risk — this is the lab result that excites me most:
Baseline hsCRP: 5.0 mg/L (high cardiovascular risk)
Month 6 hsCRP: 3.5 mg/L (moderate risk)
Month 12 hsCRP: 0.5 mg/L (low risk)
This level of inflammatory marker reduction is comparable to what you'd see with statin therapy. Combined with the weight loss, my 10-year ASCVD risk score dropped from 12% to 6%. My cardiologist is genuinely impressed.
DeniseRN_TPA 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…
I read this differently from DeniseRN_TPA, on substance rather than tone. 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.
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Browse GL BiochemDr.PainCLE said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
Continuous metabolic monitoring dashboard for cardiovascular risk — I track everything in a spreadsheet and here's the month-over-month trend for my key markers:
Weight: consistent downtrend, -2.0 lbs/week average
Fasting glucose (finger stick): stable at 89 mg/dL
Blood pressure (home): 115/75 average
Resting heart rate: 69 bpm (down from 85)
Waist circumference: down 19 inches total
The resting heart rate improvement correlates with cardiovascular fitness gains. Everything is moving in the right direction.
amsterdam_pete said:CRP reduction on cardiovascular risk — this is the lab result that excites me most: Baseline hsCRP: 5.0 mg/L (high cardiovascular risk) Month 6 hsCRP:…
Mine went the same way, slower. The detail I would add is minor and it is already implied above.