The limits of mechanism: why receptor data will not tell you who responds
The mechanism is well described. The variance is not.
Semaglutide
Page 14 of 18 of this archive, newest first.
Diminishing returns, quantified
Where the curve flattens, what flattens with it, and what does not.
Stepping down is part of titration
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
What happens when the drug is taken away: three randomised answers
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
The supply gap as a clinical event
Why the reason for stopping changes what happens afterwards.
Which results are findings and which are consequences of the weight loss
Three different explanations for the same abnormal number, and how to tell them apart.
The incretin receptors, ranked by how much we actually know about them
The receptor is expressed in more tissues than the popular account allows, and that is the whole story.
Do you need the top of the ladder?
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
Seasonal use, holiday use, and the honest state of the evidence
An absence of evidence is not evidence of harm. It is also not a licence.
What the tirzepatide schedule assumes about a person it has never met
We work the arithmetic out in full, because it is arithmetic and it is short.
Rapid weight loss moves eight analytes for reasons that have nothing to do with the drug
Three different explanations for the same abnormal number, and how to tell them apart.
Why "muscle-sparing" is a marketing term and not a measurement
The rule that a quarter of weight lost is lean tissue has been in textbooks for decades and does not survive close reading.
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.
Why people actually stop, in the order they actually stop
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
The advice is mostly reasonable. The certainty is not earned.
Almost every practical recommendation in circulation was established in a population that does not resemble the people now following it.
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.
Reading the dulaglutide titration schedule as a regulatory artefact
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.
Two-thirds back: the extension nobody expected to be the headline
The regain trajectories, arm by arm, with the estimands named.
A missed dose, modelled: what happens to liraglutide concentrations over the following fortnight
Half-life, accumulation ratio and time to steady state are three separate quantities, and confusing them produces most of the bad advice in circulation.
Not everybody regains at the same rate, and nobody knows why
Regain begins immediately, proceeds at a decelerating rate, and does not usually return to baseline within the observed follow-up. Each of those three clauses matters.