Escalating onto a rising curve
We work the arithmetic out in full, because it is arithmetic and it is short.
Semaglutide
Page 9 of 18 of this archive, newest first.
Fat mass fell more than lean mass. That is the finding, and it is not the headline.
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.
From cell to clinic: where the extrapolation stops being safe
The mechanism is well described. The variance is not.
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.
The upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
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 one-quarter rule, and the paper that took it apart
Grading six widely repeated claims against the studies actually behind them.
Continued treatment against continued placebo: the comparison that settled it
What was withdrawn, from whom, after how long, and what was measured afterwards.
Two sessions a week, and the evidence behind the prescription
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.
Vitamin D, adiposity, and a volume-of-distribution problem
Reduced intake is a plausible mechanism for deficiency. Reduced absorption is not, and the two are conflated in most of the advice.
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.
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…
The steps get smaller as the ladder gets higher, and that is deliberate
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
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.
A design note on withdrawal trials, and why the run-in matters
The regain trajectories, arm by arm, with the estimands named.
When a symptom is information and when it is noise
The practice is near-universal, clinically sensible, and supported by observational data rather than randomised comparison. We say which is which.
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 limits of mechanism: why receptor data will not tell you who responds
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
Not everybody regains at the same rate, and nobody knows why
What returns, in what order, and how much of the benefit survives.
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.