The First Twelve Weeks

Part 1 — Pharmacology

Background rates, and why they matter for attribution

The features that should prompt urgent assessment, stated once and plainly.

Part 2 — Pharmacology

Gallstones during rapid weight loss: drug, or weight loss?

We give background rates alongside trial rates, because an event occurring during treatment is not thereby caused by it.

Part 3 — Pharmacology

Escalating past the approved maximum, examined honestly

Where the curve flattens, what flattens with it, and what does not.

Part 4 — Pharmacology

Stepping down is part of titration

Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.

Part 5 — Pharmacology

Discontinuation rates, read honestly

Roughly four to seven per cent of trial participants discontinued for adverse events, mostly gastrointestinal, mostly during escalation. That is the empirical size of the…

Part 6 — Patient Notes

Attribution is the hard part

Pancreatitis is rare, was adjudicated in the outcome programmes, and did not show the imbalance early case reports suggested.

Part 7 — Patient Notes

Gallstones during rapid weight loss: drug, or weight loss?

The features that should prompt urgent assessment, stated once and plainly.

Part 8 — Pharmacology

What the trials counted as intolerance

Trial discontinuation figures are a floor, not an estimate: trial populations are supported in ways ordinary patients are not.

Part 9 — Patient Notes

Discontinuation rates, read honestly

The ceiling varies severalfold between people, and nothing measurable at baseline predicts where it sits.

Part 10 — Patient Notes

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.

Part 11 — Explainers

An error taxonomy for a market without a pharmacist

The recurring errors in this market are not exotic. They are a small set of arithmetic and reading failures, each capable of moving a dose by a factor of two or ten.

Part 12 — Explainers

Dose-limiting: a definition worth being strict about

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.