Weight regain after discontinuation (revision 10)
Old revision·00:44, 30 Dec 2024·RedirectRini
| Weight regain after discontinuationClinical practice | |
|---|---|
Randomised withdrawal designs separate regain from natural variation. | |
| Evidence design | Randomised withdrawal after a lead-in |
| Principal trials | STEP 4, SURMOUNT-4 |
| Observed pattern | Steady regain towards baseline |
| Topic infobox · conventions | |
Weight regain after discontinuation is the return of body weight towards its pre-treatment value when incretin therapy stops. It has been documented in randomised withdrawal trials, which are the design capable of distinguishing it from the natural course of weight in a treated population.[1]
In STEP 4, participants who had reached the maintenance dose during a 20-week run-in were randomised to continue or to switch to placebo. Those continuing lost further weight; those switched regained steadily over the following 48 weeks.[1]
The finding is unsurprising given the mechanism. These agents act by producing a sustained pharmacological signal in the appetite-regulating system; removing the signal removes the effect, and the circuits return to their prior state rather than being reset by the period of treatment.[2]
What the withdrawal trials show
[edit]A randomised withdrawal design is necessary because an observational comparison of people who stop with people who continue is confounded: those who stop differ systematically, often having stopped because of intolerance or lack of response.[1]
STEP 4 and SURMOUNT-4 both randomised after a lead-in on active treatment, so both groups had already lost weight and differed only in what followed. Regain in the withdrawn groups was substantial and progressive; neither trial ran long enough to establish whether weight returns fully to baseline.[1]
Cardiometabolic markers moved with weight. Improvements in blood pressure, lipids and glycaemia during the lead-in reversed on withdrawal, which argues that the benefits were weight-mediated rather than persistent effects of the exposure.[3]
Interpretation
[edit]The finding is often described as showing that treatment must be lifelong. That is a stronger claim than the trials support: they show that stopping is followed by regain over the periods studied, which is a statement about what happens rather than about what must happen.[1]
It is also not unique to this class. Weight regain follows cessation of essentially every weight-management intervention that is stopped, including diet and structured lifestyle programmes, and the pattern here resembles that literature rather than departing from it.[3]
References
- ^ a b c d e Rubino D, Abrahamsson N, Davies M, et al. "Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance (STEP 4)." JAMA 325(14):1414–1425 (2021). PMID 33755728.
- ^ Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." Cell Metabolism 27(4):740–756 (2018). PMID 29617641.
- ^ a b Wilding JPH, Batterham RL, Calanna S, et al. "Once-weekly semaglutide in adults with overweight or obesity." New England Journal of Medicine 384(11):989–1002 (2021). PMID 33567185.