Weight change after discontinuation of an incretin receptor agonist
In adults who have lost weight during treatment with an incretin receptor agonist, what happens to body weight after treatment is withdrawn?
§1Abstract
§1.1Review question
In adults who have lost weight during treatment with an incretin receptor agonist, what happens to body weight after treatment is withdrawn?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| Population | Adults who completed a defined treatment period on an incretin receptor agonist with documented weight reduction. |
| Intervention | Continued treatment. |
| Comparator | Withdrawal to placebo, with or without a continued lifestyle intervention. |
| Outcomes | Percentage change in body weight from the point of randomised withdrawal to the end of the withdrawal period; proportion returning to within 5 % of pre-treatment weight. |
§1.3Method in brief
A review of the effects of an intervention on pre-specified outcomes, with a quantitative synthesis where the contributing studies are sufficiently similar. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 20 June 2025 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.[1]
§1.4Conclusion
Moderate certainty evidence from two randomised withdrawal trials indicates that a substantial proportion of the weight lost during treatment is regained after withdrawal, and that continued treatment is required to maintain the effect. The Institute regards this as the single most decision-relevant finding in the weight-management evidence base and notes that it is systematically under-reported relative to the initial weight-loss estimates.
The conclusion rests on 17 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
§1.6Consultation
This review was released for public comment before ratification. Draft synthesis: weight change after discontinuation of an incretin receptor agonist received 16 submissions. Amendments arising are recorded in the amendment log and are traceable to a numbered submission.
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, Lingvay I, Mosenzon O, Rosenstock J, Rubio MA, Rudofsky G, Tadayon S, Wadden TA, Dicker D. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA 2021;325(14):1414–1425. doi:10.1001/jama.2021.3224 · PMID 33755728
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.