Percentage weight change as a surrogate outcome
To what extent does a change in body weight predict a change in the clinical outcomes for which weight reduction is undertaken?
§1Abstract
§1.1Review question
To what extent does a change in body weight predict a change in the clinical outcomes for which weight reduction is undertaken?
§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 with obesity. |
| Intervention | Any intervention producing weight reduction. |
| Comparator | Any. |
| Outcomes | The association between the treatment effect on weight and the treatment effect on cardiovascular events, mortality, and other clinical outcomes across trials. |
§1.3Method in brief
A review whose unit of analysis is a study characteristic rather than a treatment effect. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 17 November 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
Low certainty evidence indicates that percentage weight change is an imperfect surrogate. The Institute records two observations that constrain the inference in opposite directions: within the incretin class, the cardiovascular effect in the one trial designed to detect it emerged earlier than the weight trajectory alone would predict, and outside the class, interventions producing comparable weight change have not produced comparable cardiovascular effects. Neither observation supports treating weight change as interchangeable with clinical benefit, and the Institute grades any such conversion as an inference and marks it as one.
The conclusion rests on 24 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: Percentage weight change as a surrogate outcome received 9 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.
- Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornøe CW, Ryan DH. Semaglutide and cardiovascular outcomes in obesity without diabetes. New England Journal of Medicine 2023;389(24):2221–2232. doi:10.1056/NEJMoa2307563 · PMID 37952131
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.