Is 1 mg weekly a defensible maintenance dose for a GLP-1 receptor agonist?

What I am working with: 1 mg · a GLP-1 receptor agonist.

I am trying to build something sustainable rather than something thorough that I will abandon.

I have already decided the broad direction; this is about the specifics.

What should I decide now, and what should I defer?

1 mg a week is 0.143 mg a day averaged out and 52 mg over a year — but "defensible" is not a property of the number, it is a property of where the number came from. A maintenance dose is defensible when a trial randomised people to it and reported what happened, and indefensible when it was arrived at by interpolation between two doses that were studied. So the question to ask of 1 mg is which arm it corresponds to: if a programme ran 1 mg as a maintenance level, there is an efficacy figure, a tolerability figure and a discontinuation rate attached to it. If it sits between two studied levels, everything said about it is extrapolation, and the burden of that is on whoever proposed it. The other half of the arithmetic is supply: at 1 mg a week a 10 mg vial is 10 weeks and you will need about 6 of them a year, which is worth knowing before the dose is settled rather than after. Maintenance doses are set by a prescriber against an individual; nothing here is medical advice.

The short version: reach a working dose, hold it, and then consider whether less would hold it just as well.

Glycaemic maintenance has a faster and cleaner signal than weight maintenance, particularly with continuous monitoring, which makes the downward search more tractable when glycaemia is the endpoint.

Label titration ladders, structure only

Structure is identical across the class: small start, four-week steps, a defined maintenance range, a defined ceiling.

Mechanically, weight is a noisy signal. A rolling four-week average is the instrument; single weigh-ins after a dose reduction will show nothing interpretable.

Dose-response for weight in the trial programmes was real but flattening at the upper end, which is consistent with a lower maintenance requirement.

The lowest dose that holds the result is the answer, and it is individual.

Answering this needs the reason for the current dose, since a dose chosen for loss and a dose chosen for maintenance are different decisions.

Maintenance and loss are different endpoints. Loss requires a sustained energy deficit; maintenance requires only that the counter-regulatory drive is offset, and that may need less exposure.

Gastrointestinal tolerability generally improves on a reduced dose, which is a genuine quality-of-life argument for the search rather than only a cost one.

Nothing here is medical advice, and research-use compounds are not approved for human use.

Going back up after a short gap does not require re-titrating from the bottom.

Any reduction takes four to five weeks to express itself, so the search proceeds in months.

If the result deteriorates on a lower dose, returning to the previous one is straightforward and does not require re-titration from the bottom provided the gap has been short.

The underlying point is that the maintenance dose is not necessarily the same a year later, since the counter-regulatory response attenuates slowly if at all.

The caveat is that dose reduction is a clinical decision and this is a description of a search strategy rather than a recommendation.

The withdrawal trials answer stopping, not reducing. Different questions.

The honest answer is that the maintenance dose is individual and that the search for it is slow because the feedback is slow.

The withdrawal trials — STEP-4 and SURMOUNT-4 — established what happens when treatment stops entirely. They did not evaluate dose reduction, so the evidence for a lower maintenance dose is inference rather than data.

Gastrointestinal adverse event rates in the trials are dose-related, which supports the tolerability argument for the lowest effective dose.

Search downward, one step, eight weeks each, on a rolling average.

This is a question the trial programmes answered only partially, and it is worth saying which parts are evidenced.

A downward search proceeds one step at a time with at least eight weeks at each level, because a weekly agent takes four to five weeks to reach the new steady state and then needs time for the trend to be readable.

The counter-regulatory hormonal response to weight loss persists for at least a year after the loss, which is the physiological reason maintenance needs something rather than nothing.

Glycaemic maintenance gives a faster signal than weight maintenance.