Two-thirds back: the extension nobody expected to be the headline
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
Titration
Page 4 of 14 of this archive, newest first.
The trade has decided the ceiling is arbitrary. The trials disagree.
Where the curve flattens, what flattens with it, and what does not.
What actually helps, ranked by evidence
Dietary measures are widely recommended, plausible on mechanism, and supported mainly by observational data and clinical experience.
The escalation table is the thinnest page in the label
The published ladder exists because a protocol needed a single number. Practice has never followed it exactly, and the regulatory file never assumed it would.
The upper rungs, ranked by evidence
We looked at what the dose-ranging data supports about going higher, and it is thinner and less flattering than the market assumes.
A supply gap is a pharmacological event
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
The effect profile, predicted from an expression map
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
What happens when the drug is taken away: three randomised answers
What was withdrawn, from whom, after how long, and what was measured afterwards.
The mechanism behind the mechanism
The clinical effect profile is almost fully predictable from where the receptor is expressed, which is unusual and useful.
The mechanism behind the mechanism
The clinical effect profile is almost fully predictable from where the receptor is expressed, which is unusual and useful.
The interventions with trial support, and the much longer list without
Almost nothing in the standard management repertoire has been tested in a randomised trial in this specific population. We say what is extrapolated and from where.
Reading the semaglutide titration schedule as a regulatory artefact
The published ladder exists because a protocol needed a single number. Practice has never followed it exactly, and the regulatory file never assumed it would.
What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
Side effects, cost, supply, target: four reasons with four trajectories
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
The area postrema, and the anatomy of an unwanted effect
Delayed gastric emptying is a mechanism that becomes an adverse effect above a threshold. It is not a complication in the ordinary sense.
The incidence tables, read line by line
Almost every figure in circulation about tolerability comes from six publications. This is what they say.
Delayed emptying explains some of this, and not all of it
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
Attribution is the hard part
Rapid weight loss by any means raises gallstone risk. Separating that from a direct drug effect requires a comparator, and the trials have one.
Diminishing returns, quantified
Where the curve flattens, what flattens with it, and what does not.
Target dose, effective dose, and the distance between them
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.