Why people actually stop, in the order they actually stop
A supply interruption is a discontinuation with no notice, no taper and no plan. That is a distinct clinical situation.
Semaglutide
Page 2 of 18 of this archive, newest first.
Why a drug that acts on the pancreas changes what food tastes like
Receptor expression maps explain the effect profile better than any dose-response curve.
Target dose, effective dose, and the distance between them
What the trials measured was continuation against withdrawal. What patients want to know is continuation at a lower dose, and that study has largely not been done.
The skeleton responds to load, and load is falling
What the Journal would want measured before treating this as settled in either direction.
What we would need to randomise to answer this properly
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.
Fat mass fell more than lean mass. That is the finding, and it is not the headline.
A substudy powered to describe a mean is not a substudy powered to detect a clinically meaningful individual change.
What the tirzepatide schedule assumes about a person it has never met
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
Continued treatment against continued placebo: the comparison that settled it
The regain trajectories, arm by arm, with the estimands named.
The supplement trade found this drug class quickly, and the citations did not improve
The resistance-training and energy-deficit literature supports a higher protein intake. None of it was conducted in people taking an incretin.
What we would need to measure to explain the response distribution
The mechanism is well described. The variance is not.
The skeleton responds to load, and load is falling
Weight loss reduces bone mineral density at load-bearing sites. Whether that translates into fractures in this population is unmeasured.
The upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
What a month without the drug does to tolerability
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…
Target dose, effective dose, and the distance between them
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
REWIND was built to answer the stopping question, and it did
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
Which results are findings and which are consequences of the weight loss
A substantial proportion of the abnormal results generated during rapid weight loss are consequences of the weight loss rather than findings about the person.
One receptor, several signals: the case for reading liraglutide as a biased agonist
Receptor pharmacology explains more of the clinical picture than the dose does — and almost none of it appears in the material patients are given.
GIP was a failed target for thirty years. Then it was not.
A dual agonist is one molecule with two receptor activities. A co-formulation is two molecules in one pen. The coverage treats them as synonyms.
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.
Randomised withdrawal is the cleanest design in this field and the least discussed
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.