Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists
In adults at elevated cardiovascular risk, what is the effect of a glucagon-like peptide-1 receptor agonist compared with placebo on major adverse cardiovascular events?
§1Abstract
§1.1Review question
In adults at elevated cardiovascular risk, what is the effect of a glucagon-like peptide-1 receptor agonist compared with placebo on major adverse cardiovascular events?
§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 type 2 diabetes at elevated cardiovascular risk, or adults with overweight or obesity and established cardiovascular disease without diabetes. |
| Intervention | Any glucagon-like peptide-1 receptor agonist in an event-driven outcome trial. |
| Comparator | Placebo added to standard care. |
| Outcomes | Primary: time to first three-point major adverse cardiovascular event. Secondary: cardiovascular death, all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalisation for heart failure. |
§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 7 September 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 the class as a whole reduces major adverse cardiovascular events relative to placebo in the enrolled populations. The Institute nonetheless declines to describe the effect as a class effect: the neutral result of the lixisenatide trial and the borderline result of the extended-release exenatide trial are inconsistent with a uniform class mechanism, and the human-albumin-bound and structurally exendin-derived agents behave differently from one another. The effect is established in secondary prevention and is supported by one trial with a substantial primary-prevention population.
The conclusion rests on 11 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: Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists received 13 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
- Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsbøll T. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. New England Journal of Medicine 2016;375(19):1834–1844. doi:10.1056/NEJMoa1607141 · PMID 27633186
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