Withdrawal and Rebound
Withdrawal and rebound describe what follows stopping a drug, ranging from a simple return of the underlying condition to an overshoot past the untreated baseline or a dependence syndrome.
Three distinct phenomena get called the same thing. Loss of effect is the underlying condition reasserting itself once drug exposure falls, and it implies nothing beyond the drug having worked. Rebound is an overshoot past the untreated baseline, caused by a counter-regulatory adaptation that persists after the drug is gone. Withdrawal proper is a syndrome of new symptoms driven by physiological dependence. Half-life sets how abruptly any of them arrives.
Genuine rebound has clear examples. Abrupt beta-blocker cessation can produce tachycardia and angina exceeding pretreatment levels through upregulated receptors, and stopping clonidine suddenly can produce hypertension worse than the original. The incretin data look different. In the extension of the 68-week semaglutide obesity trial, participants regained roughly two-thirds of the weight they had lost within a year of stopping, and cardiometabolic measures drifted back toward, not beyond, their starting values.
That distinction carries the argument about chronic disease. Weight returning after discontinuation is what happens when a treatment for a chronic condition is withdrawn, in the same way blood pressure rises after an antihypertensive is stopped. It is evidence about the durability of the intervention rather than evidence that the drug stopped working or created a dependence, and it is why randomised withdrawal designs are used to test whether continued treatment is needed.
The misreading with the most traction is rebound hyperphagia framed as appetite returning worse than before treatment. Trial data show return toward baseline, not past it. The related error runs the other way: describing GLP-1 receptor agonists as addictive because stopping them has consequences, which confuses the reversal of a therapeutic effect with a withdrawal syndrome.