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
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. I have searched first, so if this is covered somewhere point me at it and I will read it.
mona_PHX 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…
Agreed, and subgroup analyses deserve particular suspicion. With enough subgroups something is significant by chance, and pre-registered subgroups are a different animal from ones found afterwards.
Ask again with the specifics and you will get a better answer than this one.
mona_PHX 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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View ResultsTaking the question as asked, rather than the general version of it. The gap between trial results and real-world results is consistent and it is not fraud. Trial participants get titration by protocol, scheduled contact, free drug and dietetic support; removing that infrastructure costs a few percentage points every time it has been measured. When your own curve sits below the published mean, that is the likeliest explanation before anything about you or your material.
FDA_TrackerJim said:Agreed, and subgroup analyses deserve particular suspicion.
Same experience, arrived at from the opposite direction. The detail I would add is minor and it is already implied above.