Exenatide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: durability of effect
In the population defined for atherosclerotic cardiovascular disease and cardiovascular risk reduction, is the effect of Exenatide maintained across the full duration of the contributing trials?
Templated review frame. This review question was generated by crossing an indication with a compound for which contributing trials exist. Its prose frame is templated and is shared with other questions of the same shape. Its included studies, its summary of findings and its certainty rating are computed from the underlying records and are not templated. The Institute publishes these questions because the alternative is to leave a question the document set can answer unanswered, and it labels them because the alternative is to present a templated frame as an authored one.
§1Abstract
§1.1Review question
In the population defined for atherosclerotic cardiovascular disease and cardiovascular risk reduction, is the effect of Exenatide maintained across the full duration of the contributing trials?
§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 | Established atherosclerotic disease of the coronary, cerebral or peripheral arterial beds, or a risk profile sufficient for enrolment in a cardiovascular outcome trial. |
| Intervention | Exenatide administered as subcutaneous twice daily (immediate release) or once weekly (poly(lactide-co-glycolide) microsphere extended release). |
| Comparator | The comparator used in each contributing trial, reported per trial rather than pooled across comparator types. |
| Outcomes | Anchor outcome for this indication: Three-point major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke). Additional outcomes: Cardiovascular death; All-cause death; 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 11 August 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.[1,2]
§1.4Conclusion
High certainty evidence bears on whether the effect of Exenatide in atherosclerotic cardiovascular disease and cardiovascular risk reduction is maintained across the randomised period. The contributing trials range in duration and the Institute reports the trajectory per trial rather than pooling across durations, because a mean at 36 weeks and a mean at 104 weeks are not estimates of the same quantity.
The conclusion rests on 3 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
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.
- Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, Chan JC, Choi J, Gustavson SM, Iqbal N, Maggioni AP, Marso SP, Öhman P, Pagidipati NJ, Poulter N, Ramachandran A, Zinman B, Hernandez AF. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine 2017;377(13):1228–1239. doi:10.1056/NEJMoa1612917 · PMID 28910237
- Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). The Lancet 2009;374(9683):39–47. doi:10.1016/S0140-6736(09)60659-0 · PMID 19515413
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