RetaRick_CA said:

Relative and absolute effects need reading together.

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.

EndoResFellow said:

My own curve sits about four points below the published mean and I spent two months assuming that meant something was wrong with me or with my…

EndoResFellow 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 metformin for T2DM prevention. That's a strong clinical argument for this approach.

JennaRN 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 0.84 (95% CI 0.67-0.84), I²=42%. This is a robust and consistent effect.

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

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

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.