SURPASS-2 was built to answer the stopping question, and it did
What was withdrawn, from whom, after how long, and what was measured afterwards.
Patient experience
First-person accounts, reported as accounts.
What we would need to randomise to answer this properly
The older-adult diet-and-exercise trials are the closest analogue to rapid pharmacological weight loss, and they are twenty years old.
The shortage years, and what they taught about interruption
The trials studied planned withdrawal. Almost nobody stops that way.
Reading the exenatide composition data without the press release
A substudy powered to describe a mean is not a substudy powered to detect a clinically meaningful individual change.
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.
What the placebo arms of the withdrawal trials actually tell us
The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately randomised it.
Seasonal use, holiday use, and the honest state of the evidence
A great deal of practice has grown up around intermittent schedules. The randomised evidence for any of them is, as far as the Journal can establish, nil.
The skeleton responds to load, and load is falling
What the Journal would want measured before treating this as settled in either direction.
What we would need to randomise to answer this properly
One randomised trial has combined a GLP-1 receptor agonist with supervised exercise. Its result is the single most useful piece of evidence in this area.
Fat mass fell more than lean mass. That is the finding, and it is not the headline.
A substudy powered to describe a mean is not a substudy powered to detect a clinically meaningful individual change.
The supply gap as a clinical event
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
Seasonal use, holiday use, and the honest state of the evidence
A great deal of practice has grown up around intermittent schedules. The randomised evidence for any of them is, as far as the Journal can establish, nil.
Continued treatment against continued placebo: the comparison that settled it
The regain trajectories, arm by arm, with the estimands named.
The imaging substudy is an afterthought in the protocol and the centrepiece of the debate
The composition data comes from imaging substudies enrolling a few score participants at selected sites. It is the best evidence available and it is thin.
Lean mass is a compartment, not a tissue
The instrument determines the answer more than the drug does, and the trade quotes the answer without naming the instrument.
Sarcopenia is a diagnosis, not a synonym for losing lean mass
The rule that a quarter of weight lost is lean tissue has been in textbooks for decades and does not survive close reading.
The shortage years, and what they taught about interruption
Why the reason for stopping changes what happens afterwards.
Why "muscle-sparing" is a marketing term and not a measurement
Grading six widely repeated claims against the studies actually behind them.
Why people actually stop, in the order they actually stop
The trials studied planned withdrawal. Almost nobody stops that way.
What the older diet-and-exercise trials found in the hip
The evidence base is one secondary analysis, several small studies and a large amount of extrapolation from bariatric surgery.