Reflux, early satiety, and the volume the stomach will accept
A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.
Pharmacology in 2024
Page 4 of 5 of this archive, newest first.
Non-responders, and the honest state of the evidence about them
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
A missed dose, modelled: what happens to retatrutide concentrations over the following fortnight
An accumulation model, drawn from published parameters, with its assumptions stated.
A schedule that bends does not break
Every major phase 3 protocol in this class allowed escalation to be delayed for tolerability. Almost no product label explains the mechanics of doing so.
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.
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.
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.