What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
Recent work
121 piecesWhat the anaesthetists said, and then said again
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.
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.
Why a 0.036-dalton difference is the hardest number in peptide identity
Every instrument specification quoted in an advertisement is a best case obtained on a calibration mixture, not on a submitted vial.
Peak capacity, and the honest measure of a separation
Gradient slope is the single most consequential method parameter for a reported purity figure, and it is the one most often omitted.
Adverse events by dose, adverse events by week
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.
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.
Where the receptor is: a tissue-by-tissue account of liraglutide’s reach
The central effects are not a bonus. On the current evidence they are the principal mechanism of weight loss.
Gastric emptying is a mechanism, not a side effect
The central effects are not a bonus. On the current evidence they are the principal mechanism of weight loss.
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.
Reading a barrel: the graduation that is not the one you think
The graduation interval differs between barrel sizes, and a 1 mL barrel is frequently marked in two-unit steps. Reading one as though it were marked in single units halves…
What the tirzepatide schedule assumes about a person it has never met
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
The mechanism behind the mechanism
Delayed gastric emptying is a mechanism that becomes an adverse effect above a threshold. It is not a complication in the ordinary sense.
The upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
Target dose, effective dose, and the distance between them
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
The imaging substudy is an afterthought in the protocol and the centrepiece of the debate
The composition data comes from imaging substudies enrolling a few score participants at selected sites. It is the best evidence available and it is thin.
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 named analyst is the cheapest quality signal in this trade
Somebody has to be answerable for a release document. On most certificates in this market, nobody is named at all.
How a peptide that lasts seven days binds a receptor that recycles in minutes
What the in-vitro data supports, what it does not, and where the extrapolation to a person begins.
Accreditation, scope, and the question nobody asks VendorInvestigate
Two signatures — one who performed the work, one who approved its release — are the ordinary regulated convention and are almost unknown here.