Diminishing returns, quantified
Escalation beyond the label is common in this market. Reporting that it happens is not the same as reporting that it works.
Titration
Page 5 of 14 of this archive, newest first.
Not everybody regains at the same rate, and nobody knows why
The variance around the mean regain trajectory is large and unexplained, exactly as it is for the weight loss.
What the placebo arms of the withdrawal trials actually tell us
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
Severity grading, and the gap between a grade and an experience
Severity in these tables is graded by interference with activity, not by how unpleasant the experience was. Those are different measurements.
Forty-four per cent: reading the nausea figure properly
Trial adverse-event tables count episodes reported to a study nurse. They are the best data we have and they systematically under-record the mundane.
Background rates, and why they matter for attribution
Pancreatitis is rare, was adjudicated in the outcome programmes, and did not show the imbalance early case reports suggested.
The shortage years, and what they taught about interruption
Why the reason for stopping changes what happens afterwards.
Continued treatment against continued placebo: the comparison that settled it
The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately randomised it.
What the trial protocols permitted, and what the labels omitted
Reducing a dose is not going backwards. In a tolerability-limited class it is the mechanism by which the ceiling is found.
Do you need the top of the ladder?
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.
The interventions with trial support, and the much longer list without
The intervention with the clearest evidence is the one nobody frames as an intervention: adjusting the dose.
Diminishing returns, quantified
Where the curve flattens, what flattens with it, and what does not.
The interventions with trial support, and the much longer list without
Dietary measures are widely recommended, plausible on mechanism, and supported mainly by observational data and clinical experience.
Every fortnight, every third week, seasonally: an unstudied practice
What the exposure arithmetic says about a fortnightly schedule, and where the arithmetic stops being informative.
What the trials counted as intolerance
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.
The lowest effective dose is a real concept with almost no data behind it
What the labels permit, what clinicians do, and the size of the gap between them.
Discontinuation rates, read honestly
The ceiling varies severalfold between people, and nothing measurable at baseline predicts where it sits.
Pancreatitis, obstruction, gallbladder: three things nausea can be
Rapid weight loss by any means raises gallstone risk. Separating that from a direct drug effect requires a comparator, and the trials have one.
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.
When a symptom is information and when it is noise
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.