pete_manc_UK said:

The gap between trial results and real-world results is consistent and it is not fraud.

Pushing back on pete_manc_UK here. 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.

NauseaFreeNow said:

I keep finding that the number in the press summary and the number in the paper are not the same number, and the difference is always in the same…

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 MI incidence (HR 0.78) over 4 years of follow-up[1].

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

kate.chem said:

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

kate.chem said:

...regarding the trial evidence...

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

A recent meta-analysis of 15 RCTs (n=12,300) found that the trial evidence was associated with a clinically meaningful effect size across diverse patient populations[1].

The NNT was 12, which is comparable to antihypertensives for stroke reduction. That's a strong clinical argument for this approach.

Following on from ben_calgary — and this may be the naive question:

How long did you give it before you decided it was working?

OP back with an update, since a thread like this is useless without one.

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.