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 population was selected and supported in ways a real cohort is not, so I would read the effect size as a ceiling rather than an expectation.
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. I would rather have one careful answer than five confident ones.
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…
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, -2.3 lbs/week average
Fasting glucose (finger stick): stable at 88 mg/dL
Blood pressure (home): 118/74 average
Resting heart rate: 68 bpm (down from 84)
Waist circumference: down 18 inches total
The resting heart rate improvement correlates with cardiovascular fitness gains. Everything is moving in the right direction.
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…
Pushing back on Dr.RaviCardio here. 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.
That is the short version; the long version is somebody else's post.
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View ResultsBenResearch_OR said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
Mendelian randomization evidence supporting GLP-1 pathway modulation for cardiovascular risk: genetic variants in the GLP1R gene region associated with lower BMI also show associations with reduced cardiovascular risk, confirming a causal pathway[1].
This "natural experiment" (people born with genetically higher GLP-1 signaling being leaner and healthier) provides orthogonal evidence supporting the pharmacological approach. When genetic epidemiology, clinical trials, and mechanistic studies all converge, confidence in the therapeutic approach is high.
[1] Zheng SL, et al. Lancet Diabetes Endocrinol. 2023;11(12):869-879.
labquiet_amy said:Continuous metabolic monitoring dashboard for cardiovascular risk — I track everything in a spreadsheet and here's the month-over-month trend for my…
This matches mine closely enough to be worth saying so out loud.