Dr.AddMedPHL said:

Read four things before the headline number.

Pushing back on Dr.AddMedPHL 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.

hannah_MT 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…

hannah_MT 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 statins for secondary prevention. That's a strong clinical argument for this approach.

LarryQC_SD said:

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

Bayesian meta-analysis perspective on the trial evidence: traditional frequentist meta-analyses report point estimates and confidence intervals. Bayesian approaches provide probability distributions that are more intuitive for clinical decision-making.

For example: "There is a 98.5% probability that semaglutide 2.4mg produces >10% weight loss vs placebo" is more actionable than "RR 3.4, 95% CI 2.8-4.1, p<0.001."

The the trial evidence evidence is strong under both frameworks, but Bayesian analysis better communicates the degree of certainty for individual patient counseling.

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

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

Reporting back.

Follow-up: I read the paper rather than the summary and the qualifier I was missing was in the second paragraph of the results.