Dr.MetabolicMD said:The gap between trial results and real-world results is consistent and it is not fraud.
Dr.MetabolicMD said:...regarding the trial evidence...
I think this is an underappreciated point. To expand on it with some data:
A recent meta-analysis of 18 RCTs (n=15,600) found that the trial evidence was associated with a robust effect size across diverse patient populations[1].
The NNT was 15, which is comparable to statins for secondary prevention. That's a strong clinical argument for this approach.
One thing that is still open after VanRx_Mike’s answer:
How would you tell the difference between that and the alternative explanation?
dan_philly said:Dr.MetabolicMD said: ...regarding the trial evidence...
Forest plot interpretation for the the trial evidence meta-analysis: when reading the pooled estimate, pay attention to:
- Point estimate (HR/RR/OR) — center of the diamond
- Confidence interval width — precision of the estimate
- I² statistic — heterogeneity across studies
- Individual study weights — are results driven by one large trial?
- Prediction interval — range of plausible true effects in future settings
The the trial evidence meta-analysis shows a pooled RR of 0.83 (95% CI 0.72-0.83), I²=41%. This is a robust and consistent effect.
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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.
Dr.ObesityMed said:Forest plot interpretation for the the trial evidence meta-analysis: when reading the pooled estimate, pay attention to: Point estimate (HR/RR/OR) —…
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 25,000 GLP-1 users vs matched controls showed reduced all-cause mortality (HR 0.81) over 5 years of follow-up[1].
These results complement the RCT data and suggest the benefits translate to real-world populations.
[1] Registry-based cohort study, pre-print 2024.