SURMOUNT-4 was built to answer the stopping question, and it did
The regain trajectories, arm by arm, with the estimands named.
Tirzepatide
A once-weekly dual GIP/GLP-1 receptor agonist, studied for glycaemic control in SURPASS and for weight in SURMOUNT.
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.
The restart nobody plans for
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
The trade has decided the ceiling is arbitrary. The trials disagree.
Where the curve flattens, what flattens with it, and what does not.
The dose that got you here and the dose that keeps you here
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
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 withdrawal trials, read as designs rather than warnings
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
The eighteenth month, and the conversation that should have happened in the third
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
Do you need the top of the ladder?
Two withdrawal-design trials tell us what happens when treatment stops. Neither tells us what the lowest effective maintenance dose is.
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.
Side effects, cost, supply, target: four reasons with four trajectories
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
Steady state is not a metaphor — it is an arithmetic fact about exenatide
What the pharmacokinetic data supports about dose timing, missed doses and interruption.
Side effects, cost, supply, target: four reasons with four trajectories
The trials studied planned withdrawal. Almost nobody stops that way.
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.
The eighteenth month, and the conversation that should have happened in the third
Two withdrawal-design trials tell us what happens when treatment stops. Neither tells us what the lowest effective maintenance dose is.
Escalating past the approved maximum, examined honestly
We looked at what the dose-ranging data supports about going higher, and it is thinner and less flattering than the market assumes.
Reading HbA1c in the presence of anaemia
The alternatives with shorter windows, what they measure, and why they are rarely ordered.
What STEP 2 tells us about maintenance, and what it does not
What the labels permit, what clinicians do, and the size of the gap between them.