What a month without the drug does to tolerability
Concentrations fall by half a week, so a month away leaves a small fraction of steady state. Resuming at the previous dose presents the receptor with a step it has not seen…
Pharmacology
Incretin pharmacology reported from the primary literature: receptor selectivity and bias, pharmacokinetics and steady state, the difference between a dual agonist and a co-formulation, and the mechanisms behind the effects patients notice first.
Everything filed here
What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
The trade has decided the ceiling is arbitrary. The trials disagree.
Where the curve flattens, what flattens with it, and what does not.
Seven days, four weeks, one number: how liraglutide exposure actually accumulates
Half-life, accumulation ratio and time to steady state are three separate quantities, and confusing them produces most of the bad advice in circulation.
Do you need the top of the ladder?
Two withdrawal-design trials tell us what happens when treatment stops. Neither tells us what the lowest effective maintenance dose is.
What the anaesthetists said, and then said again
What endoscopic and ultrasound studies found about residual gastric content, and what the aspiration data does and does not support.
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 tolerability data everybody quotes and nobody reads
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.
Antiemetics, laxatives and the thin literature underneath them
We separate what is supported, what is reasonable, and what is folklore, and we do not pretend the boundaries are crisp.
The eighteenth month, and the conversation that should have happened in the third
Two withdrawal-design trials tell us what happens when treatment stops. Neither tells us what the lowest effective maintenance dose is.
What the GIP receptor adds: reading cagrilintide as two drugs in one sequence
Head-to-head data exists for some of these comparisons and not for others. This piece says which.
Forty-four per cent: reading the nausea figure properly
Almost every figure in circulation about tolerability comes from six publications. This is what they say.
The area postrema, and the anatomy of an unwanted effect
What scintigraphy and breath-test studies established about emptying rate, and what they did not.
The upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
Beta-arrestin, cAMP, and the part of cagrilintide’s mechanism nobody quotes
Selectivity, potency and efficacy are three different measurements. The trade routinely reports none of them.
Adverse events by dose, adverse events by week
Almost every figure in circulation about tolerability comes from six publications. This is what they say.
Why a drug that acts on the pancreas changes what food tastes like
Receptor expression maps explain the effect profile better than any dose-response curve.
What the trials counted as intolerance
The ceiling varies severalfold between people, and nothing measurable at baseline predicts where it sits.
Target dose, effective dose, and the distance between them
What the trials measured was continuation against withdrawal. What patients want to know is continuation at a lower dose, and that study has largely not been done.
Holding the dose before surgery: for whom, for how long
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.