The kidney, the heart and the receptor nobody was looking for
The same receptor population that produces the therapeutic effect produces the commonest adverse one.
Priya Ramanathan, PharmD
Page 5 of 7 of this archive, newest first.
Archive — page 5
131 piecesThe supply gap as a clinical event
The trials studied planned withdrawal. Almost nobody stops that way.
Disregard limits: what a regulated laboratory does with a tiny peak
Chromatographic software does not integrate every fluctuation in the baseline. It applies a threshold, and the threshold changes the reported purity by amounts that matter…
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.
Everything a buyer assumes has been checked, ranked by whether it has
A purity figure is silent on peptide content, on water, on counter-ion, on sterility, on endotoxin and on stability. Each of those silences has a price attached.
Randomised withdrawal is the cleanest design in this field and the least discussed
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
Discontinuation rates, read honestly
Roughly four to seven per cent of trial participants discontinued for adverse events, mostly gastrointestinal, mostly during escalation. That is the empirical size of the…
GIP was a failed target for thirty years. Then it was not.
The glucagon arm raises energy expenditure and also raises hepatic glucose output. Balancing those is the whole engineering problem.
The GLP-1 receptor is not a switch, and retatrutide is not a key
Receptor pharmacology explains more of the clinical picture than the dose does — and almost none of it appears in the material patients are given.
Hydration, protein and the two failures that compound each other
Almost nothing in the standard management repertoire has been tested in a randomised trial in this specific population. We say what is extrapolated and from where.
How much water: the question with no single right answer
A more concentrated reconstitution means smaller injection volumes, which means larger proportional errors from graduation, dead space and technique.
Where the receptor is: a tissue-by-tissue account of tirzepatide’s reach
The same receptor population that produces the therapeutic effect produces the commonest adverse one.
From cell to clinic: where the extrapolation stops being safe
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
Gallstones during rapid weight loss: drug, or weight loss?
Pancreatitis is rare, was adjudicated in the outcome programmes, and did not show the imbalance early case reports suggested.
The lowest effective dose is a real concept with almost no data behind it
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
Two-thirds back: the extension nobody expected to be the headline
What was withdrawn, from whom, after how long, and what was measured afterwards.
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.
Two decimal places on a single injection is a rhetorical choice
The arithmetic of significant figures, applied to a document that routinely reports four of them.
What a 1 mL syringe does that a 0.3 mL syringe does not
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…
The supply gap as a clinical event
Why the reason for stopping changes what happens afterwards.