A reference post rather than a discussion. Corrections are the point; I would rather this be right than mine. It is about cardiovascular outcomes, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
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.
The condition it depends on
The qualification that SELECT enrolled a secondary-prevention population. Extrapolating a 20% relative reduction to a healthy 35-year-old with a BMI of 31 is not what that trial showed.
The practical version
Relative versus absolute is the distinction that gets lost: a 20% relative reduction on a high baseline risk is a large absolute benefit, and the same relative figure on a low baseline risk is a small one.
What I am not sure about
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. Numbers rather than impressions, if you have them.
tony_orlando 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…
CRP reduction on cardiovascular risk — this is the lab result that excites me most:
Baseline hsCRP: 11.0 mg/L (high cardiovascular risk)
Month 6 hsCRP: 3.5 mg/L (moderate risk)
Month 12 hsCRP: 0.4 mg/L (low risk)
This level of inflammatory marker reduction is comparable to what you'd see with statin therapy. Combined with the weight loss, my 10-year ASCVD risk score dropped from 18% to 6%. My cardiologist is genuinely impressed.
tony_orlando 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 tony_orlando, 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.
I would rather be corrected than agreed with, if it comes to it.
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Browse GL BiochemDr.GastroMayo said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
Dr.GastroMayo 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.
BenResearch_OR said:CRP reduction on cardiovascular risk — this is the lab result that excites me most: Baseline hsCRP: 11.0 mg/L (high cardiovascular risk) Month 6…
This matches mine closely enough to be worth saying so out loud.