This gets cited here weekly, usually second-hand, so it is worth setting out what it does and does not establish.
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 completion rate deserves as much attention as the headline, because a large effect among those who finished is a different claim from a large effect among those enrolled.
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. If the honest answer is that nobody knows, that is a useful answer and I would rather have it.
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.
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…
Cardiac biomarkers and cardiovascular risk: my cardiologist ordered advanced cardiac labs given my family history. Results were encouraging:
- NT-proBNP: 71 pg/mL (normal, cardiac function preserved)
- Lp(a): 61 nmol/L (genetic, unchanged — expected)
- ApoB: dropped from 151 to 96 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.
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…
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.
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View ResultsBethLabQueen said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
I'm 58 years old and want to share my perspective on cardiovascular risk as an older member of this community.
My doctor was initially hesitant because of my age, but the SELECT trial included patients up to 72 and showed consistent benefit across age groups. We started at the lowest dose with closer monitoring.
11 months later: down 58 lbs, off atorvastatin, A1C from 7.6% to 5.3%. My cardiologist is thrilled. cardiovascular risk is absolutely relevant for older adults — don't let anyone tell you otherwise.
TrialNerd_Beth said:Cardiac biomarkers and cardiovascular risk: my cardiologist ordered advanced cardiac labs given my family history.
Can confirm. Same sequence, different timescale. Posting only so the count is not one.