TrialTracker_MD said:

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

TrialTracker_MD 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.

A narrower follow-up, since the general answer is now clear:

What would you measure differently if you were starting again?

labquiet_amy said:

TrialTracker_MD said: ...regarding the trial evidence...

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 12,000 GLP-1 users vs matched controls showed reduced heart failure hospitalization (HR 0.74) over 3 years of follow-up[1].

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

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

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

Dr.LeslieOBGYN said:

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

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 0.75 (95% CI 0.69-0.90), I²=48%. This is a robust and consistent effect.