{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:49:48Z","timestamp":1789609788550,"version":"build-2803163510"},"reference-count":44,"publisher":"Elsevier BV","issue":"15","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jacc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["JACC"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1016\/j.jacc.2026.01.013","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T14:05:38Z","timestamp":1773237938000},"page":"1936-1949","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Designing Next-Generation Cardiometabolic Outcome Trials for Obesity Medicines"],"prefix":"10.1016","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-0710","authenticated-orcid":false,"given":"Elke","family":"Platz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Peikert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-0253","authenticated-orcid":false,"given":"Biykem","family":"Bozkurt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Van der Schueren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildiko","family":"Lingvay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren K.","family":"McGuire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-1570","authenticated-orcid":false,"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-2593","authenticated-orcid":false,"given":"Naveed","family":"Sattar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jacc.2026.01.013_bib2","doi-asserted-by":"crossref","first-page":"e535","DOI":"10.1161\/CIR.0000000000000450","article-title":"Contributory risk and management of comorbidities of hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in chronic heart failure: a scientific statement from the American Heart Association","volume":"134","author":"Bozkurt","year":"2016","journal-title":"Circulation"},{"issue":"4","key":"10.1016\/j.jacc.2026.01.013_bib4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1004578","article-title":"The cardiology community begins to embrace obesity as an important target for cardiovascular health","volume":"22","author":"Sattar","year":"2025","journal-title":"PLoS Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib5","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S2213-8587(24)00363-2","article-title":"Estimating direct tissue effects versus weight loss effects of incretin-based drugs for obesity on various chronic conditions","volume":"13","author":"Sattar","year":"2025","journal-title":"Lancet Diabetes Endocrinol"},{"key":"10.1016\/j.jacc.2026.01.013_bib6","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1056\/NEJMoa1212914","article-title":"Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes","volume":"369","author":"Look","year":"2013","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib7","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1161\/CIRCULATIONAHA.120.052386","article-title":"Bariatric surgery and cardiovascular outcomes in patients with obesity and cardiovascular disease: a population-based retrospective cohort study","volume":"143","author":"Doumouras","year":"2021","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2026.01.013_bib8","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1056\/NEJMoa1003114","article-title":"Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects","volume":"363","author":"James","year":"2010","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib9","doi-asserted-by":"crossref","first-page":"846","DOI":"10.2337\/dc24-1533","article-title":"Cardiovascular and kidney outcomes and mortality with long-acting injectable and oral glucagon-like peptide 1 receptor agonists in individuals with type 2 diabetes: a systematic review and meta-analysis of randomized trials","volume":"48","author":"Lee","year":"2025","journal-title":"Diabetes Care"},{"key":"10.1016\/j.jacc.2026.01.013_bib10","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1056\/NEJMoa2307563","article-title":"Semaglutide and cardiovascular outcomes in obesity without diabetes","volume":"389","author":"Lincoff","year":"2023","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib11","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1161\/CIR.0000000000001186","article-title":"A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: a scientific statement from the American Heart Association","volume":"148","author":"Ndumele","year":"2023","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2026.01.013_bib12","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1016\/S0140-6736(25)01375-3","article-title":"Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial","volume":"406","author":"Deanfield","year":"2025","journal-title":"Lancet"},{"key":"10.1016\/j.jacc.2026.01.013_bib13","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1067\/mhj.2001.117511","article-title":"Pounds of prevention: obesity therapy","volume":"142","author":"Patel","year":"2001","journal-title":"Am Heart J"},{"key":"10.1016\/j.jacc.2026.01.013_bib14","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1056\/NEJM199708283370901","article-title":"Valvular heart disease associated with fenfluramine-phentermine","volume":"337","author":"Connolly","year":"1997","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib15","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0140-6736(10)60935-X","article-title":"Rimonabant for Prevention of Cardiovascular Events (CRESCENDO): a randomised, multicentre, placebo-controlled trial","volume":"376","author":"Topol","year":"2010","journal-title":"Lancet"},{"key":"10.1016\/j.jacc.2026.01.013_bib17","series-title":"Keynote lecture: FDA\u2019s Offce of Cardiology, Hematology, Endocrinology, and Nephrology: From Founding to Present Day and Beyond","author":"Joffe","year":"2024"},{"key":"10.1016\/j.jacc.2026.01.013_bib18","series-title":"Guideline on clinical evaluation of medicinal products used in weight management","year":"2016"},{"key":"10.1016\/j.jacc.2026.01.013_bib19","unstructured":"Committee for Medicinal Products for Human Use. Reflection paper on assessment of cardiovascular safety profile of medicinal products. European Medicines Agency. EMA\/CHMP\/50549\/2015."},{"key":"10.1016\/j.jacc.2026.01.013_bib20","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1056\/NEJMoa1808721","article-title":"Cardiovascular safety of lorcaserin in overweight or obese patients","volume":"379","author":"Bohula","year":"2018","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib21","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1056\/NEJMp2003873","article-title":"Cancer risk associated with lorcaserin: the FDA's review of the CAMELLIA-TIMI 61 trial","volume":"383","author":"Sharretts","year":"2020","journal-title":"N Engl J Med"},{"issue":"1","key":"10.1016\/j.jacc.2026.01.013_bib22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jacc.2024.04.022","article-title":"Semaglutide and NT-proBNP in obesity-related HFpEF: insights from the STEP-HFpEF program","volume":"84","author":"Petrie","year":"2024","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.jacc.2026.01.013_bib23","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s12933-022-01601-w","article-title":"Transitioning to active-controlled trials to evaluate cardiovascular safety and efficacy of medications for type 2 diabetes","volume":"21","author":"McGuire","year":"2022","journal-title":"Cardiovasc Diabetol"},{"issue":"24","key":"10.1016\/j.jacc.2026.01.013_bib24","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1056\/NEJMoa2505928","article-title":"Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes","volume":"393","author":"Nicholls","year":"2025","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib25","doi-asserted-by":"crossref","first-page":"4391","DOI":"10.1093\/eurheartj\/ehaa665","article-title":"The win ratio approach for composite endpoints: practical guidance based on previous experience","volume":"41","author":"Redfors","year":"2020","journal-title":"Eur Heart J"},{"key":"10.1016\/j.jacc.2026.01.013_bib26","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1093\/eurheartj\/ehad083","article-title":"Anthropometric measures and adverse outcomes in heart failure with reduced ejection fraction: revisiting the obesity paradox","volume":"44","author":"Butt","year":"2023","journal-title":"Eur Heart J"},{"key":"10.1016\/j.jacc.2026.01.013_bib27","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.isci.2019.10.062","article-title":"Disparity in adiposity among adult with normal body mass index and waist-to-height ratio","volume":"21","author":"Dybala","year":"2019","journal-title":"iScience"},{"key":"10.1016\/j.jacc.2026.01.013_bib28","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S2213-8587(24)00316-4","article-title":"Definition and diagnostic criteria of clinical obesity","volume":"13","author":"Rubino","year":"2025","journal-title":"Lancet Diabetes Endocrinol"},{"key":"10.1016\/j.jacc.2026.01.013_bib29","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2023-078523","article-title":"Trends in cardiovascular disease incidence among 22 million people in the UK over 20 years: population based study","volume":"385","author":"Conrad","year":"2024","journal-title":"BMJ"},{"issue":"1","key":"10.1016\/j.jacc.2026.01.013_bib30","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.cardfail.2024.07.001","article-title":"HF STATS 2024: heart failure epidemiology and outcomes statistics, an updated 2024 report from the Heart Failure Society of America","volume":"31","author":"Bozkurt","year":"2024","journal-title":"J Card Fail"},{"key":"10.1016\/j.jacc.2026.01.013_bib31","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1161\/CIRCHEARTFAILURE.112.972828","article-title":"Predictors of new-onset heart failure: differences in preserved versus reduced ejection fraction","volume":"6","author":"Ho","year":"2013","journal-title":"Circ Heart Fail"},{"key":"10.1016\/j.jacc.2026.01.013_bib32","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1093\/eurheartj\/ehaf057","article-title":"Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction: the PARAGON-HF trial","volume":"46","author":"Peikert","year":"2025","journal-title":"Eur Heart J"},{"key":"10.1016\/j.jacc.2026.01.013_bib33","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1016\/S0140-6736(24)00469-0","article-title":"Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials","volume":"403","author":"Butler","year":"2024","journal-title":"Lancet"},{"key":"10.1016\/j.jacc.2026.01.013_bib34","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1056\/NEJMoa2410027","article-title":"Tirzepatide for heart failure with preserved ejection fraction and obesity","volume":"392","author":"Packer","year":"2025","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib35","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1056\/NEJMoa2306963","article-title":"Semaglutide in patients with heart failure with preserved ejection fraction and obesity","volume":"389","author":"Kosiborod","year":"2023","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib36","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1056\/NEJMoa2313917","article-title":"Semaglutide in patients with obesity-related heart failure and type 2 diabetes","volume":"390","author":"Kosiborod","year":"2024","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib37","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1161\/CIRCULATIONAHA.120.045888","article-title":"Glucagon-like peptide 1 receptor agonists and heart failure: the need for further evidence generation and practice guidelines optimization","volume":"142","author":"Khan","year":"2020","journal-title":"Circulation"},{"key":"10.1016\/j.jacc.2026.01.013_bib38","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1001\/jama.2016.10260","article-title":"Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial","volume":"316","author":"Margulies","year":"2016","journal-title":"JAMA"},{"key":"10.1016\/j.jacc.2026.01.013_bib39","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/ejhf.657","article-title":"Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial","volume":"19","author":"Jorsal","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"10.1016\/j.jacc.2026.01.013_bib40","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1603827","article-title":"Liraglutide and cardiovascular outcomes in type 2 diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib41","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/S0140-6736(24)01498-3","article-title":"Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial","volume":"404","author":"Deanfield","year":"2024","journal-title":"Lancet"},{"issue":"12","key":"10.1016\/j.jacc.2026.01.013_bib42","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1016\/j.jchf.2024.09.004","article-title":"Survodutide for the treatment of obesity: rationale and design of the SYNCHRONIZE Cardiovascular Outcomes Trial","volume":"12","author":"Kosiborod","year":"2024","journal-title":"JACC Heart Fail"},{"key":"10.1016\/j.jacc.2026.01.013_bib43","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/S0140-6736(25)00509-4","article-title":"Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial","volume":"405","author":"Bonaca","year":"2025","journal-title":"Lancet"},{"key":"10.1016\/j.jacc.2026.01.013_bib44","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1038\/s41591-024-03223-z","article-title":"Integrating liver endpoints in clinical trials of cardiovascular and kidney disease","volume":"30","author":"Zannad","year":"2024","journal-title":"Nat Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib45","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1056\/NEJMra1510062","article-title":"Master protocols to study multiple therapies, multiple diseases, or both","volume":"377","author":"Woodcock","year":"2017","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jacc.2026.01.013_bib46","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1002\/ejhf.2853","article-title":"The win ratio method in heart failure trials: lessons learnt from EMPULSE","volume":"25","author":"Pocock","year":"2023","journal-title":"Eur J Heart Fail"},{"key":"10.1016\/j.jacc.2026.01.013_bib48","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1001\/jama.2016.1558","article-title":"Effect of naltrexone-bupropion on major adverse cardiovascular events in overweight and obese patients with cardiovascular risk factors: a randomized clinical trial","volume":"315","author":"Nissen","year":"2016","journal-title":"JAMA"}],"container-title":["JACC"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0735109726000768?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0735109726000768?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T19:54:06Z","timestamp":1782849246000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0735109726000768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":44,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["S0735109726000768"],"URL":"https:\/\/doi.org\/10.1016\/j.jacc.2026.01.013","relation":{},"ISSN":["0735-1097"],"issn-type":[{"value":"0735-1097","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Designing Next-Generation Cardiometabolic Outcome Trials for Obesity Medicines","name":"articletitle","label":"Article Title"},{"value":"JACC","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jacc.2026.01.013","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 by the American College of Cardiology Foundation. Published by Elsevier.","name":"copyright","label":"Copyright"}]}}