Glucagon-like peptide-1 receptor agonists for weight reduction in adults with obesity
In adults with obesity and without type 2 diabetes, what is the effect of a glucagon-like peptide-1 receptor agonist compared with placebo on percentage change in body weight at the primary analysis timepoint?
§1Abstract
§1.1Review question
In adults with obesity and without type 2 diabetes, what is the effect of a glucagon-like peptide-1 receptor agonist compared with placebo on percentage change in body weight at the primary analysis timepoint?
§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 aged 18 years and above with a body-mass index of 30 kg/m² or above, or 27 kg/m² or above with at least one weight-related comorbidity, and without type 2 diabetes at randomisation. |
| Intervention | Any glucagon-like peptide-1 receptor agonist administered at a dose evaluated in a confirmatory trial, with or without a concurrent lifestyle intervention. |
| Comparator | Placebo administered with the same lifestyle intervention. |
| Outcomes | Primary: percentage change in body weight from baseline to the pre-specified primary analysis timepoint. Secondary: proportion achieving reductions of 5 %, 10 %, 15 % and 20 %; change in waist circumference; change in systolic blood pressure; discontinuation for adverse events. |
§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 25 May 2024 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.[1,2]
§1.4Conclusion
High certainty evidence indicates that glucagon-like peptide-1 receptor agonists reduce body weight substantially more than placebo over 56 to 104 weeks, with a placebo-subtracted effect that differs by agent and by dose across roughly a threefold range. The certainty is high for the existence and approximate magnitude of the effect and lower for its persistence beyond the randomised period, for which the only randomised evidence comes from withdrawal designs and points to substantial regain.
The conclusion rests on 12 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: glucagon-like peptide-1 receptor agonists for weight reduction, version 2 received 15 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.
- Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF. Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine 2021;384(11):989–1002. doi:10.1056/NEJMoa2032183 · PMID 33567185
- Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet 2021;397(10278):971–984. doi:10.1016/S0140-6736(21)00213-0 · PMID 33667417
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