Tirzepatide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: tolerability and discontinuation
In the population defined for atherosclerotic cardiovascular disease and cardiovascular risk reduction, what is the incidence of adverse events leading to discontinuation with Tirzepatide compared with its comparator?
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, what is the incidence of adverse events leading to discontinuation with Tirzepatide compared with its comparator?
§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 | Tirzepatide administered as subcutaneous once weekly. |
| 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 harms, in which the absence of an event in a trial of conventional size is treated as uninformative rather than as reassurance. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 5 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
Moderate certainty evidence from 2 contributing trials bears on tolerability. Discontinuation for adverse events is reported in the summary-of-findings table alongside the efficacy outcomes rather than in an annex, because a trial reporting a given effect with high discontinuation is reporting a materially different result from one reporting the same effect with high persistence.
The conclusion rests on 2 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.
- Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A. Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine 2022;387(3):205–216. doi:10.1056/NEJMoa2206038 · PMID 35658024
- Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad NN, Bunck MC, Benabbad I, Zhang XM. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet 2023;402(10402):613–626. doi:10.1016/S0140-6736(23)01200-X · PMID 37385275
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