What actually helps, ranked by evidence
Dietary measures are widely recommended, plausible on mechanism, and supported mainly by observational data and clinical experience.
Pharmacology — 2025
Receptors, exposure, and what the molecules actually do.
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.
Why receptor selectivity is the least discussed number in incretin pharmacology
The class is described as though every molecule in it did the same thing. At the receptor, they demonstrably do not.
The glucagon receptor arm, and why it is the hardest to reason about
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.
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.
Non-responders, and the honest state of the evidence about them
The mechanism is well described. The variance is 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.