Read the primary source rather than the write-up and the two do not agree, so here is what is actually in 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.
The narrow version of the question 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.
RickReta_CO 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: 61 pg/mL (normal, cardiac function preserved)
- Lp(a): 41 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.
RickReta_CO 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…
Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. 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.SurgeonPGH said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
Dizziness and cardiovascular risk: I was lightheaded for the first 2 weeks. Root cause was a combination of reduced caloric intake and mild dehydration.
Fix: minimum 80-100oz water daily, don't skip meals even if you're not hungry (eat small protein-rich snacks), and stand up slowly from sitting/lying positions. Also check your blood pressure — GLP-1-induced weight loss can make BP meds too strong, requiring dose reduction.
LabKate said:Cardiac biomarkers and cardiovascular risk: my cardiologist ordered advanced cardiac labs given my family history.
This is my experience too, for whatever a second data point is worth. Posting only so the count is not one.