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.
Explainers
Page 8 of 12 of this archive, newest first.
Page 8
Albumin, fatty-acid chains, and the engineering that made a weekly incretin possible
An accumulation model, drawn from published parameters, with its assumptions stated.
Choosing a needle for a subcutaneous peptide
Gauge affects pain and flow rate rather than depth. A finer needle is more comfortable and slower, and with a viscous solution the difference is noticeable.
Is semaglutide better than dulaglutide, or differently balanced?
What adding GIP activity does, on the current evidence, and what remains unresolved.
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…
The reproducible spectrum: the single most useful thing a report can carry
What the Journal asks for when it writes to a supplier about an identity claim, and how often it gets it.
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.
Constipation is the one that responds best to boring measures
Dietary measures are widely recommended, plausible on mechanism, and supported mainly by observational data and clinical experience.
What STEP 4 and SURMOUNT-4 actually established
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
Units, millilitres, milligrams: three scales on one small object
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…
Non-responders, and the honest state of the evidence about them
A catalogue of open questions, with an assessment of how likely each is to be resolved.
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.
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.
The label says four weeks. The clinic says whatever holds.
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.
Discontinuation rates, read honestly
Trial discontinuation figures are a floor, not an estimate: trial populations are supported in ways ordinary patients are not.
Reading a barrel in the wrong increments
Almost every case involves a change — a new vial, a new syringe size, a new supplier — carried forward with an old number.
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.
Accumulation, trough, and the exposure curve nobody draws for patients
An accumulation model, drawn from published parameters, with its assumptions stated.