Diminishing returns, quantified
Where the curve flattens, what flattens with it, and what does not.
Delphine Ruzek
Page 4 of 7 of this archive, newest first.
Archive — page 4
121 piecesDelayed emptying explains some of this, and not all of it
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
Units, millilitres, milligrams: three scales on one small object
We work through the arithmetic in full, because it is short, and because the errors it prevents are order-of-magnitude errors.
The effect profile, predicted from an expression map
A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.
Gallstones during rapid weight loss: drug, or weight loss?
A small number of serious gastrointestinal events occur in people taking these drugs. Distinguishing them from the expected effect profile is the most consequential…
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.
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 mechanism behind the mechanism
A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.
Two sessions a week, and the evidence behind the prescription
The older-adult diet-and-exercise trials are the closest analogue to rapid pharmacological weight loss, and they are twenty years old.
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 eighteenth month, and the conversation that should have happened in the third
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
Sarcopenia is a diagnosis, not a synonym for losing lean mass
Almost every practical recommendation in circulation was established in a population that does not resemble the people now following it.
What the trials counted as intolerance
The ceiling varies severalfold between people, and nothing measurable at baseline predicts where it sits.
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.
Attribution is the hard part
Pancreatitis is rare, was adjudicated in the outcome programmes, and did not show the imbalance early case reports suggested.
Two decimal places on a single injection is a rhetorical choice
A result without a specification is a number. A specification without a result is a promise. Certificates in this market frequently carry one and not the other.
One measurement, twenty companies, forty compounds
A market that competes on one measurement will optimise that measurement. There are legitimate ways to raise a purity figure that involve no change to the product at all.
The mechanism behind the mechanism
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
The word “confirmed” is doing an enormous amount of work on this certificate
An intact mass measurement establishes elemental composition, at best. The number of distinct sequences consistent with a given composition is astronomically large.