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.
Pharmacology in 2025
Page 3 of 5 of this archive, newest first.
Three receptors, one peptide: the design problem behind triple agonism
What adding GIP activity does, on the current evidence, and what remains unresolved.
Is liraglutide better than mazdutide, or differently balanced?
What adding GIP activity does, on the current evidence, and what remains unresolved.
Antiemetics, laxatives and the thin literature underneath them
Constipation is the most tractable of the effects and the most consistently under-managed.
The mechanism behind the mechanism
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
When to stop escalating and when to stop entirely
The ceiling varies severalfold between people, and nothing measurable at baseline predicts where it sits.
Gastric emptying is a mechanism, not a side effect
The central effects are not a bonus. On the current evidence they are the principal mechanism of weight loss.
What the trials counted as intolerance
Trial discontinuation figures are a floor, not an estimate: trial populations are supported in ways ordinary patients are not.
The restart nobody plans for
We work through the residual-exposure table so the decision can be made from numbers rather than from feel.
The mechanism behind the mechanism
The clinical effect profile is almost fully predictable from where the receptor is expressed, which is unusual and useful.
From cell to clinic: where the extrapolation stops being safe
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
The eighteenth month, and the conversation that should have happened in the third
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 mechanism behind the mechanism
The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of this drug class is where it is, and it is…
The label says four weeks. The clinic says whatever holds.
Deviation from the printed ladder is not non-compliance. In this class it is the modal behaviour of competent prescribing.
The interventions with trial support, and the much longer list without
The intervention with the clearest evidence is the one nobody frames as an intervention: adjusting the dose.
The mechanism behind the mechanism
Delayed gastric emptying is a mechanism that becomes an adverse effect above a threshold. It is not a complication in the ordinary sense.
From cell to clinic: where the extrapolation stops being safe
Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader questions live.
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.
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.