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ForumsPublic SquareIs there a ceiling effect for GLP-1-mediated weight loss? — my results so far Page 2

Is there a ceiling effect for GLP-1-mediated weight loss? — my results so far

raj_cambridge Mon, Dec 15, 2025 at 6:20 AM 33 replies 1,411 viewsPage 2 of 7
sarah.morrison
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Dec 15, 2025 at 7:55 AM#6
BenResearch_OR 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.

35 5josh_phd_bmore, roxy_nash, tony_orlando and 32 others
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dan_philly
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Dec 15, 2025 at 8:32 AM#7
raj_cambridge 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…
raj_cambridge 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.

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traveltech_sara
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Dec 15, 2025 at 9:09 AM#8
sarah.morrison 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.

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ZaraB_AL
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Dec 15, 2025 at 9:46 AM#9

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

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

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raj_cambridge
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Dec 15, 2025 at 12:43 PM#10

Closing the loop on my own question.

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.

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