Why the fifth week of a dulaglutide dose feels different from the first
An accumulation model, drawn from published parameters, with its assumptions stated.
Semaglutide
Page 12 of 18 of this archive, newest first.
Sarcopenia is a diagnosis, not a synonym for losing lean mass
The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.
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.
What the placebo arms of the withdrawal trials actually tell us
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
The shortage years, and what they taught about interruption
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
The kidney, the heart and the receptor nobody was looking for
The central effects are not a bonus. On the current evidence they are the principal mechanism of weight loss.
Sarcopenia is a diagnosis, not a synonym for losing lean mass
The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.
The upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
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.
What we would need to randomise to answer this properly
The older-adult diet-and-exercise trials are the closest analogue to rapid pharmacological weight loss, and they are twenty years old.
Maximum tolerated is not maximum approved
Weight reduction in the long programmes flattens at roughly sixty to seventy-two weeks. The timing is consistent, predictable and almost never mentioned in advance.
Two sessions a week, and the evidence behind the prescription
The recommendation survives scrutiny. The reasoning offered for it frequently does not.
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.
Side effects, cost, supply, target: four reasons with four trajectories
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
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 dose that got you here and the dose that keeps you here
The commonest real-world strategy in this drug class is the least studied one.
Why the bone question is harder than the muscle question
Density is a proxy for strength and an imperfect one, particularly when soft-tissue thickness over the measurement site is changing.
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.
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.
The out-of-range flag is a statistical convention with a printer attached
A flag is a probability statement about a population. It is not a statement about the person holding the printout.