Adverse events by dose, adverse events by week
Almost every figure in circulation about tolerability comes from six publications. This is what they say.
Pharmacology
Page 3 of 12 of this archive, newest first.
Page 3
Reading the receptor: what distinguishes cagrilintide from survodutide at the molecular level
A tour of what happens in the thirty seconds after binding, and why it matters at week thirty.
Holding a dose is a decision, not a failure
A dose held long enough stops being a pause and becomes a maintenance decision. That transition is rarely made explicitly.
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
We separate what is supported, what is reasonable, and what is folklore, and we do not pretend the boundaries are crisp.
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.
GIP was a failed target for thirty years. Then it was not.
A dual agonist is one molecule with two receptor activities. A co-formulation is two molecules in one pen. The coverage treats them as synonyms.
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…
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.
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 a month without the drug does to tolerability
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
Do you need the top of the ladder?
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
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…
Why the fifth week of a semaglutide dose feels different from the first
An accumulation model, drawn from published parameters, with its assumptions stated.