LipidDoc_ATL said:

Relative and absolute effects need reading together.

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. I would add the less popular caveat: these trial populations under-represented several groups, older adults and the highest BMI categories among them. The results probably generalise, and "probably" should be stated as an assumption rather than dropped.

Dr.CardioMD said:

My own curve sits about four points below the published mean and I spent two months assuming that meant something was wrong with me or with my…

Propensity score matching studies and the trial evidence: when RCTs aren't available for a specific question, propensity score-matched observational studies can provide useful evidence.

A recent PSM study of 18,000 GLP-1 users vs matched controls showed reduced stroke risk (HR 0.82) over 4 years of follow-up[1].

These results complement the RCT data and suggest the benefits translate to real-world populations.

RetaRick_CA said:

I would add the less popular caveat: these trial populations under-represented several groups, older adults and the highest BMI categories among them.

RetaRick_CA said:

...regarding the trial evidence...

I think this is an underappreciated point. To expand on it with some data:

A recent meta-analysis of 12 RCTs (n=8,400) found that the trial evidence was associated with a significant effect size across diverse patient populations[1].

The NNT was 8, which is comparable to antihypertensives for stroke reduction. That's a strong clinical argument for this approach.

One thing that is still open after paige_pharma’s answer:

How would you tell the difference between that and the alternative explanation?

Closing the loop on my own question.

Update — my curve sits below the published mean and the explanation is that the trial arm had support I do not have. That was reassuring rather than otherwise.