Indication assessment · §2
Atherosclerotic cardiovascular disease and cardiovascular risk reduction — evidence across compounds
Every compound the Institute assesses in atherosclerotic cardiovascular disease and cardiovascular risk reduction, with its certainty rating.
§2Evidence across compounds
Every compound the Institute assesses in this indication, with the effect as recorded, the certainty rating and the contributing trials. Effects are reported on the anchor outcome where the contributing trials measured it and on the outcome the trial actually reported where they did not.
Table 1. Compounds assessed in atherosclerotic cardiovascular disease and cardiovascular risk reduction, ordered by certainty.
| Compound | Effect as recorded | Interval as reported | Certainty | Trials |
|---|---|---|---|---|
| DulaglutideGLP-1 receptor agonist, Fc-fusion protein | MACE hazard ratio 0.88 in a population with a majority without established cardiovascular disease | HR 0.88 (95 % CI 0.79 to 0.99); 12.0 % versus 13.4 % over median 5.4 years | High | 1 |
| ExenatideGLP-1 receptor agonist (exendin-based, short- and… | MACE hazard ratio 0.91 — non-inferior to placebo but not superior | HR 0.91 (95 % CI 0.83 to 1.00); p = 0.06 for superiority | High | 1 |
| LiraglutideGLP-1 receptor agonist (acylated, once-daily) | MACE hazard ratio 0.87 in type 2 diabetes at high cardiovascular risk | HR 0.87 (95 % CI 0.78 to 0.97); 13.0 % versus 14.9 % over median 3.8 years | High | 1 |
| LixisenatideGLP-1 receptor agonist (exendin-based, short-acting) | MACE hazard ratio 1.02 — neutral | HR 1.02 (95 % CI 0.89 to 1.17) | High | 1 |
| SemaglutideGLP-1 receptor agonist (acylated, long-acting) | Three-point MACE hazard ratio 0.80 in adults with overweight or obesity and established cardiovascular disease without diabetes | HR 0.80 (95 % CI 0.72 to 0.90); 6.5 % versus 8.0 % over a mean 39.8 months | High | 2 |
| Semaglutide, oralGLP-1 receptor agonist, oral formulation with absorption… | MACE hazard ratio 0.79 (non-inferiority design) in PIONEER 6; 0.86 in the event-driven SOUL trial | PIONEER 6 HR 0.79 (95 % CI 0.57 to 1.11); SOUL HR 0.86 (95 % CI 0.77 to 0.96) | Moderate | 2 |
| SS-31 (elamipretide)Mitochondria-targeted cardiolipin-binding tetrapeptide | A phase 2 trial in ST-elevation myocardial infarction did not reduce infarct size | negative result | Moderate | 1 |
| TirzepatideDual GIP and GLP-1 receptor agonist (acylated) | MACE hazard ratio 0.92 versus dulaglutide 1.5 mg in an active-controlled non-inferiority design | HR 0.92 (95 % CI 0.83 to 1.01) | Moderate | 1 |
| HexarelinGrowth-hormone secretagogue, non-selective ghrelin receptor… | No randomised human evidence identified | — | Very low | 0 |
| TB-500Acetylated heptapeptide fragment of thymosin beta-4 | No randomised controlled human trial identified | — | Very low | 0 |
| Thymosin beta-443-residue actin-sequestering polypeptide | Phase 1 safety study completed; no efficacy conclusion | — | Very low | 1 |
| Estimates in this table are not on a common scale and must not be subtracted from one another. Where a comparison between two compounds has been made directly, it appears in a synthesis and not here. | ||||
Moderate or high certaintyLow or very low certainty
§2.1Syntheses bearing on this indication
- Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists — High
- Percentage weight change as a surrogate outcome — Low
- Cardiovascular benefit in primary compared with secondary prevention — Moderate
- Exenatide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: effect on the anchor outcome — High
- Dulaglutide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: effect on the anchor outcome — High
- Semaglutide, oral in atherosclerotic cardiovascular disease and cardiovascular risk reduction: effect on the anchor… — Moderate
- Semaglutide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: effect on the anchor outcome — High
- Tirzepatide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: effect on the anchor outcome — Moderate
- Exenatide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: tolerability and discontinuation — High
- Dulaglutide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: tolerability and… — High
- Semaglutide, oral in atherosclerotic cardiovascular disease and cardiovascular risk reduction: tolerability and… — Moderate
- Semaglutide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: tolerability and… — High
- Tirzepatide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: tolerability and… — Moderate
- Exenatide in atherosclerotic cardiovascular disease and cardiovascular risk reduction: durability of effect — High
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.
- Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Rydén L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet 2019;394(10193):121–130. doi:10.1016/S0140-6736(19)31149-3 · PMID 31189511
- Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. The Lancet Diabetes & Endocrinology 2018;6(4):275–286. doi:10.1016/S2213-8587(18)30024-X · PMID 29397376
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.
Compound Evidence Institute · CEI-IN-03/2 · https://compoundevidence.com/indications/cvd/evidence/ · retrieved 30 July 2026