SarahChen_PharmD said:

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

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.

DadBodDave 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…

DadBodDave 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.

TrialNerd_Beth said:

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

Forest plot interpretation for the the trial evidence meta-analysis: when reading the pooled estimate, pay attention to:

1. Point estimate (HR/RR/OR) — center of the diamond
2. Confidence interval width — precision of the estimate
3. I² statistic — heterogeneity across studies
4. Individual study weights — are results driven by one large trial?
5. Prediction interval — range of plausible true effects in future settings

The the trial evidence meta-analysis shows a pooled RR of 0.76 (95% CI 0.65-0.86), I²=34%. This is a robust and consistent effect.

One thing that is still open after BrianDallas92’s answer:

What did you change at the same time, and can you separate the two now?

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.