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 5 of 5 of this archive, newest first.
The glucagon receptor arm, and why it is the hardest to reason about
What adding GIP activity does, on the current evidence, and what remains unresolved.
How a peptide that lasts seven days binds a receptor that recycles in minutes
A tour of what happens in the thirty seconds after binding, and why it matters at week thirty.
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…
Holding a dose is a decision, not a failure
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
When to stop escalating and when to stop entirely
An effect is dose-limiting when it prevents adequate intake, prevents normal activity, or produces a risk of its own. Discomfort alone is not the test.
What the trials counted as intolerance
We set out the questions that distinguish a symptom to manage from a dose to change.
The interventions with trial support, and the much longer list without
Almost nothing in the standard management repertoire has been tested in a randomised trial in this specific population. We say what is extrapolated and from where.
Holidays, surgery, sickness: interruption in practice
Supply interruption is the commonest cause of unplanned re-titration in this market, and it is almost never framed that way.
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.