Why your endoscopist wants to know about your injection
This is the single interaction with ordinary medical care that patients most need to disclose, and it is the one most often not asked about.
Pharmacology
Page 11 of 12 of this archive, newest first.
Page 11
Holidays, surgery, sickness: interruption in practice
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
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.
Diminishing returns, quantified
The ceiling in this class is anatomical: the same receptor populations that suppress appetite provoke nausea, and they saturate together.
What the GLP-1 receptor actually does when mazdutide binds it
Selectivity, potency and efficacy are three different measurements. The trade routinely reports none of them.
Background rates, and why they matter for attribution
Rapid weight loss by any means raises gallstone risk. Separating that from a direct drug effect requires a comparator, and the trials have one.
From 0.25 to 2.4: reading a ladder as a series of ratios
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
Gallstones during rapid weight loss: drug, or weight loss?
We give background rates alongside trial rates, because an event occurring during treatment is not thereby caused by it.
The glucagon receptor arm, and why it is the hardest to reason about
Head-to-head data exists for some of these comparisons and not for others. This piece says which.
The label says four weeks. The clinic says whatever holds.
What the regulatory dossiers actually contain on dose selection is remarkably thin, and worth knowing before treating the ladder as settled science.
The trade has decided the ceiling is arbitrary. The trials disagree.
The ceiling in this class is anatomical: the same receptor populations that suppress appetite provoke nausea, and they saturate together.
A supply gap is a pharmacological event
One omitted dose is a labelling question. Four omitted doses is a clinical one. The two are routinely conflated.
Severity grading, and the gap between a grade and an experience
Trial adverse-event tables count episodes reported to a study nurse. They are the best data we have and they systematically under-record the mundane.
What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
Escalating past the approved maximum, examined honestly
Where the curve flattens, what flattens with it, and what does not.
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.
Why receptor selectivity is the least discussed number in incretin pharmacology
Selectivity, potency and efficacy are three different measurements. The trade routinely reports none of them.
Albumin, fatty-acid chains, and the engineering that made a weekly incretin possible
The molecular engineering that turned a peptide with a two-minute half-life into a once-weekly drug.
Target dose, effective dose, and the distance between them
Two withdrawal-design trials tell us what happens when treatment stops. Neither tells us what the lowest effective maintenance dose is.
Stepping down is part of titration
The practice is near-universal, clinically sensible, and supported by observational data rather than randomised comparison. We say which is which.