The incretin receptors, ranked by how much we actually know about them
Selectivity, potency and efficacy are three different measurements. The trade routinely reports none of them.
Explainers in 2025
Page 4 of 5 of this archive, newest first.
Why purity is the cheapest number to flatter
The Journal has read several hundred certificates from twenty companies. The number is almost always there; the method behind it almost never is.
Site selection when the tissue has already changed
The evidence base here is the insulin injection-technique literature, which is large and transfers well on tissue questions.
The specification sheet says 500,000. The report says conforms.
Calibration drift is real, unremarkable, and the reason serious laboratories run internal standards.
Vagal afferents, the area postrema, and the anatomy of nausea
A tour of the tissues where the receptor is expressed, and what happens in each.
Mapping a rotation that you will actually follow
Repeated injection into the same small area produces lipohypertrophy — thickened, rubbery subcutaneous tissue with blunted and erratic absorption. It is common, it is…
The arithmetic behind every identity confirmation, worked in full
A peptide has a monoisotopic mass and an average mass, they differ by several daltons at this molecular size, and a certificate that does not say which it quotes cannot be…
Three receptors, one peptide: the design problem behind triple agonism
Head-to-head data exists for some of these comparisons and not for others. This piece says which.
When a symptom is information and when it is noise
A dose held long enough stops being a pause and becomes a maintenance decision. That transition is rarely made explicitly.
Do you need the top of the ladder?
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
The incidence tables, read line by line
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.
Six things incretin pharmacology cannot currently predict
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
How a correct calculation becomes a wrong dose
A pharmacist catches most of these in licensed practice. In this market there is no pharmacist, so the checks have to be structural.
Delayed emptying explains some of this, and not all of it
What scintigraphy and breath-test studies established about emptying rate, and what they did not.
The restart nobody plans for
We work through the residual-exposure table so the decision can be made from numbers rather than from feel.
A number without a suitability record is a number from an unknown instrument
System suitability is the set of checks demonstrating that the instrument and method were performing adequately when your sample was injected. It is recorded as a matter of…
What a purity certificate is silent about
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.
Tolerability is the ceiling, and the ceiling is personal
Trial discontinuation figures are a floor, not an estimate: trial populations are supported in ways ordinary patients are not.
What the GLP-1 receptor actually does when tirzepatide binds it
The class is described as though every molecule in it did the same thing. At the receptor, they demonstrably do not.
Amylin is not an incretin, and cagrilintide is not a GLP-1 agonist
The glucagon arm raises energy expenditure and also raises hepatic glucose output. Balancing those is the whole engineering problem.