Is there a ceiling effect for GLP-1-mediated weight loss? — looking for input

Short answer first, then the reasoning. Read four things before the headline number. The population, because trial populations are selected and supported in ways that real cohorts are not. The comparator, because "better than placebo" and "better than the current standard" are different claims and get reported identically. The primary endpoint as pre-registered, because a secondary endpoint promoted after the fact is a hypothesis rather than a finding. And the completion rate, because a large effect in the half of participants who finished is a different result from a large effect in everybody enrolled.

InsuranceTom said:

Read four things before the headline number.

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 0.72-0.89), I²=57%. This is a robust and consistent effect.

VanRx_Mike 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…

Same position here, arrived at the long way round. Relative and absolute effects need reading together. A 20% relative reduction on a high baseline risk is a large absolute benefit; the same relative figure on a low baseline risk is a small one, and press summaries almost always quote the relative number because it is bigger.

From the other side of the consultation, briefly.

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 all-cause mortality (HR 0.81) over 3 years of follow-up[1].

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