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 comparator does most of the work in how this gets reported, and it is not the comparator most people think they are citing.
What I actually want to know is 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.
dan_philly 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…
dan_philly said:...we're creating a generation dependent on cardiovascular risk...
I understand the concern, but consider this analogy: are we "creating a generation dependent on" blood pressure medication? Cholesterol medication? Thyroid medication?
Obesity is a chronic disease with biological drivers. Treating it with medication is no different from treating any other chronic condition. The "dependency" framing implies weakness or moral failure — neither of which is accurate.
If ongoing medication is what keeps someone healthy, that's successful treatment, not dependency.
dan_philly 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 dan_philly, 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.LipidDallas said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
Lp(a) and cardiovascular risk: a nuance that matters. Unlike most lipid markers, Lp(a) is 90%+ genetically determined and doesn't really change with weight loss or GLP-1 therapy.
My Lp(a) has remained at 45 nmol/L across all time points. If yours is elevated (>50 nmol/L), you need additional risk mitigation strategies regardless of your GLP-1 response. Don't assume your medication is covering all cardiovascular risk factors.
Dr.SportsMedIN said:dan_philly said: ...we're creating a generation dependent on cardiovascular risk...
Can confirm. Same sequence, different timescale. The detail I would add is minor and it is already implied above.