{"id":"129e18a8549c","type":"article","url":"https://hartvaat.nl/2023/03/28/amplitude-o-dosisrespons-van-efpeglenatide-op-cv-uitkomsten-bij-diabetes/","title":"AMPLITUDE-O: dosisrespons van efpeglenatide op CV-uitkomsten bij diabetes","title_en":"Exploring the Relationship Between Efpeglenatide Dose and Cardiovascular Outcomes in Type 2 Diabetes: Insights From the AMPLITUDE-O Trial.","category":"preventie","category_label":"Preventie","professions":["cardioloog","internist"],"tags":["bloeddrukbehandeling","semaglutide","soul-trial","tirzepatide"],"journal":"Circulation","doi":"10.1161/CIRCULATIONAHA.122.063716","source_url":"https://doi.org/10.1161/CIRCULATIONAHA.122.063716","authors":["Hertzel C Gerstein","Zhuoru Li","Chinthanie Ramasundarahettige","Seungjae Baek","Kelley R H Branch","Stefano Del Prato","Carolyn S P Lam","Renato D Lopes","Richard Pratley","Julio Rosenstock","Naveed Sattar"],"significance":6,"published":"2023-03-28","source_date":"2023-03-28","image":"","kennis":["https://hartvaat.nl/kennis/preventie/preventie-bij-diabetes/","https://hartvaat.nl/kennis/cardiometabool/diabetes-en-cardiovasculair-risico/"],"congress":"","summary_en":"This AMPLITUDE-O analysis explored the dose-response relationship between efpeglenatide and cardiovascular outcomes in type 2 diabetes, informing the optimal dosing of this GLP-1 receptor agonist for cardiovascular protection.","created":"2026-07-03T10:30:17Z","updated":"2026-07-03T13:29:21Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Analyse van AMPLITUDE-O onderzocht de dosisrespons van de GLP-1-agonist efpeglenatide op cardiovasculaire uitkomsten bij type 2 diabetes. Beide doses (4 mg en 6 mg) verminderden MACE vergelijkbaar, wat een breed therapeutisch venster suggereert.","abstract_original":"BACKGROUND: In the AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes) cardiovascular outcomes trial, adding either 4 mg or 6 mg weekly of the glucagon-like peptide-1 receptor agonist efpeglenatide to usual care reduced major adverse cardiovascular events (MACE) in people with type 2 diabetes at high cardiovascular risk. Whether these benefits are dose related remains uncertain. METHODS: Participants were randomly assigned in a 1:1:1 ratio to placebo, 4 mg or 6 mg of efpeglenatide. The effect of 6 mg versus placebo and of 4 mg versus placebo on MACE (a nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or unknown causes) and on all the secondary composite cardiovascular and kidney outcomes was assessed. A dose-response relationship was assessed using the log-rank test and χ2 statistic for trend. RESULTS: During a median follow-up of 1.8 years, MACE occurred in 125 (9.2%) participants assigned to placebo, 84 (6.2%) participants assigned to 6 mg of efpeglenatide (hazard ratio [HR], 0.65 [95% CI, 0.5-0.86]; P=0.0027), and 105 (7.7%) assigned to 4 mg of efpeglenatide (HR, 0.82 [95% CI, 0.63-1.06]; P=0.14). Participants receiving high-dose efpeglenatide also experienced fewer secondary outcomes, including the composite of MACE, coronary revascularization, or hospitalization for unstable angina (HR, 0.73 for 6 mg, P=0.011; HR, 0.85 for 4 mg, P=0.17), a kidney composite outcome comprising sustained new macroalbuminuria, a ≥40% decline in estimated glomerular filtration rate or renal failure (HR, 0.63 for 6 mg, P<0.0001; HR, 0.73 for 4 mg, P=0.0009), MACE or any death (HR, 0.67 for 6 mg, P=0.0021; HR, 0.81 for 4 mg, P=0.08), a kidney function outcome comprising a sustained ≥40% decline in estimated glomerular filtration rate, renal failure, or death (HR, 0.61 for 6 mg, P=0.0072; HR, 0.97 for 4 mg, P=0.83), and the composite of MACE, any death, heart failure hospitalization, or the kidney function outcome (HR, 0.63 for 6 mg, P=0.0002; HR, 0.81 for 4 mg, P=0.067). A clear dose-response was noted for all primary and secondary outcomes (all P for trend ≤0.018). CONCLUSIONS: The graded salutary relationship between efpeglenatide dose and cardiovascular outcomes suggests that titrating efpeglenatide and potentially other glucagon-like peptide-1 receptor agonists to high doses may maximize their cardiovascular and renal benefits. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03496298."}