Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.
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 am trying to establish 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.
Dr.CardioMD 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…
Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off amlodipine entirely! My cardiologist is thrilled.
If you're on BP meds and losing weight on a GLP-1, monitor your BP at home regularly. Hypotension symptoms (dizziness, lightheadedness when standing) mean your BP meds may need reduction. Don't wait for your next scheduled appointment — call your doctor.
Dr.CardioMD 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.CardioMD 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.
Correct me if the detail matters more than I have assumed.
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View ResultsDr.SurgeonPGH said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
Dr.SurgeonPGH 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.
PurityPaulOR said:Positive "side effect" of cardiovascular risk: my blood pressure dropped so much that I'm now off amlodipine entirely!
Can confirm. Same sequence, different timescale. The detail I would add is minor and it is already implied above.