Accepted answer
Week 6 is day 42: on a four-week ladder that is week 2 of dose step 2, and — at the seven-day half-life this class runs on — 6 half-lives in. Steady state is about five half-lives, so day 35 is where the concentration stops climbing on its own. Day 42 is 1 weeks past it, which means the level is no longer the variable. That distinction is most of the question: at week 2 of a step, an effect that is still accumulating is indistinguishable from one that is not resolving unless you know which side of day 35 you are on. Nausea in this class tracks the rate of change more than the level: the trial programmes report it clustered in the fortnight after each step and decaying across the weeks that follow, which is why the week number is worth locating on the ladder before anything else. Dose decisions are made under supervision, and nothing here is medical advice.
The honest answer is that it usually settles within one to two weeks at a stable dose, and that the exceptions are the reason to have a clinician.
Tolerance develops through receptor desensitisation over one to two weeks at a stable dose. Escalating before that has happened resets the process, which is the mechanism behind most miserable titrations.
Gastrointestinal adverse events, indicative pooled rates
| Event | Active arm | Placebo arm | Timing |
|---|
| Nausea | 40–45 % | 15–20 % | Peaks 1–2 wk after each step |
| Vomiting | 15–25 % | 5–8 % | Follows nausea |
| Diarrhoea | 20–30 % | 10–15 % | Early, variable |
| Constipation | 20–25 % | 8–12 % | Later onset, persistent |
| Discontinuation for GI events | 4–7 % | 1–2 % | Mostly during escalation |
Ranges span agents and doses; read the specific prescribing information for a specific figure.
Alcohol is poorly tolerated in this context for two reasons — delayed emptying alters absorption kinetics, and it irritates a stomach already under strain.
Tachyphylaxis of the gastric-emptying effect with continued exposure is documented for the long-acting agents and is the mechanistic basis for tolerance.
Smaller meals, less fat, stop at first fullness, fluids between meals.
Thank you — this is the answer I was looking for. – sian_llewellyn 9 months ago 8I would add a sentence about when to stop managing it and start seeing someone. – m_haraldsen 7 months ago add a comment