Percentage of loss, absolute kilograms, and the sleight of hand between them
The trials measured mass. Nobody measured whether the participants got weaker.
Semaglutide
Page 11 of 18 of this archive, newest first.
The supply gap as a clinical event
Why the reason for stopping changes what happens afterwards.
The one randomised trial that combined an incretin with supervised exercise
One randomised trial has combined a GLP-1 receptor agonist with supervised exercise. Its result is the single most useful piece of evidence in this area.
Dual, triple, co-formulated: a taxonomy the coverage keeps collapsing
The glucagon arm raises energy expenditure and also raises hepatic glucose output. Balancing those is the whole engineering problem.
Randomised withdrawal is the cleanest design in this field and the least discussed
The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately randomised it.
Non-responders, and the honest state of the evidence about them
The mechanism is well described. The variance is not.
What we would need to measure to explain the response distribution
The mechanism is well described. The variance is not.
Load, not cardio: the distinction the general advice keeps losing
The older-adult diet-and-exercise trials are the closest analogue to rapid pharmacological weight loss, and they are twenty years old.
Three weeks off is a fresh start, whether or not you want one
Concentrations fall by half a week, so a month away leaves a small fraction of steady state. Resuming at the previous dose presents the receptor with a step it has not seen…
Least significant change: the number your body-composition printout omits
The compartment called lean mass contains water, glycogen, viscera and skin. Only some of it is the tissue anybody is worried about.
The limits of mechanism: why receptor data will not tell you who responds
A catalogue of open questions, with an assessment of how likely each is to be resolved.
What changing your injection day does to tirzepatide exposure, and what it does not
What the pharmacokinetic data supports about dose timing, missed doses and interruption.
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.
The shortage years, and what they taught about interruption
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
Albumin, fatty-acid chains, and the engineering that made a weekly incretin possible
An accumulation model, drawn from published parameters, with its assumptions stated.
The lead-in, the randomisation, and the year that followed
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
Why no trial in this class has reported a strength endpoint
The composition data comes from imaging substudies enrolling a few score participants at selected sites. It is the best evidence available and it is thin.
Why a drug that acts on the pancreas changes what food tastes like
A tour of the tissues where the receptor is expressed, and what happens in each.
Is semaglutide better than dulaglutide, or differently balanced?
What adding GIP activity does, on the current evidence, and what remains unresolved.
What has to change before a change has happened
A flag is a probability statement about a population. It is not a statement about the person holding the printout.