Maintenance dosing: what is licensed, what is practised, and what is evidenced
What the labels permit, what clinicians do, and the size of the gap between them.
Semaglutide
A once-weekly GLP-1 receptor agonist, the subject of the STEP obesity programme and the SELECT cardiovascular outcome trial.
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.
The ceiling is a tolerability finding, not an efficacy one
We looked at what the dose-ranging data supports about going higher, and it is thinner and less flattering than the market assumes.
What we would need to randomise to answer this properly
The older-adult diet-and-exercise trials are the closest analogue to rapid pharmacological weight loss, and they are twenty years old.
Seven days, four weeks, one number: how liraglutide exposure actually accumulates
Half-life, accumulation ratio and time to steady state are three separate quantities, and confusing them produces most of the bad advice in circulation.
The one randomised trial that combined an incretin with supervised exercise
Mass and function are different endpoints and training affects them differently. Most coverage treats them as one.
The shortage years, and what they taught about interruption
The trials studied planned withdrawal. Almost nobody stops that way.
What the trials monitored, and what that implies about routine practice
The argument for a baseline panel is that it makes every subsequent result interpretable. The argument against frequent monitoring is that noise accumulates faster than…
What STEP 4 and SURMOUNT-4 actually established
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
GIP was a failed target for thirty years. Then it was not.
What adding GIP activity does, on the current evidence, and what remains unresolved.
Side effects, cost, supply, target: four reasons with four trajectories
The trials studied planned withdrawal. Almost nobody stops that way.
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.
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.
What the trials monitored, and what that implies about routine practice
Timing is the whole of the post-cessation panel: draw it too early and it measures the treatment period.
Where the receptor is: a tissue-by-tissue account of liraglutide’s reach
The central effects are not a bonus. On the current evidence they are the principal mechanism of weight loss.
The upper rungs, ranked by evidence
Where the curve flattens, what flattens with it, and what does not.
Side effects, cost, supply, target: four reasons with four trajectories
Why the reason for stopping changes what happens afterwards.
The supply gap as a clinical event
Why the reason for stopping changes what happens afterwards.
Beta-arrestin, cAMP, and the part of cagrilintide’s mechanism nobody quotes
Selectivity, potency and efficacy are three different measurements. The trade routinely reports none of them.
What STEP 4 and SURMOUNT-4 actually established
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.