Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics.

Background: Tirzepatide, a once-weekly GIP/GLP-1 receptor agonist, reduces blood glucose and body weight in people with type 2 diabetes. The cardiovascular (CV) safety and efficacy of tirzepatide have not been definitively assessed in a cardiovascular outcomes trial.
Methods: Tirzepatide is being studied in a randomized, double-blind, active-controlled CV outcomes trial. People with type 2 diabetes aged ≥40 years, with established atherosclerotic CV disease, HbA1c ≥7% to ≤10.5%, and body mass index ≥25 kg/m ² were randomized 1:1 to once weekly subcutaneous injection of either tirzepatide up to 15 mg or dulaglutide 1.5 mg. The primary outcome is time to first occurrence of any major adverse cardiovascular event (MACE), defined as CV death, myocardial infarction, or stroke. The trial is event-driven and planned to continue until ≥1,615 participants experience an adjudication-confirmed component of MACE. The primary analysis is noninferiority for time to first MACE of tirzepatide vs dulaglutide by demonstrating an upper confidence limit <1.05, which will also confirm superiority vs a putative placebo, and also to determine whether tirzepatide produces a greater CV benefit than dulaglutide (superiority analysis).
Results: Over 2 years, 13,299 people at 640 sites in 30 countries across all world regions were randomized. The mean age of randomized participants at baseline was 64.1 years, diabetes duration 14.7 years, HbA1c 8.4%, and BMI 32.6 kg/m ² . Overall, 65.0% had coronary disease, of whom 47.3% reported prior myocardial infarction and 57.4% had prior coronary revascularization. 19.1% of participants had a prior stroke and 25.3% had peripheral artery disease. The trial is fully recruited and ongoing.
Conclusion: SURPASS-CVOT will provide definitive evidence as to the CV safety and efficacy of tirzepatide as compared with dulaglutide, a GLP-1 receptor agonist with established CV benefit.
Competing Interests: Conflict of interest SJN reports grants or contracts from Amgen, Anthera Pharmaceuticals, AstraZeneca, Cerenis Therapeutics, CSL Behring, Eli Lilly and Company, Esperion Therapeutics, Infraredx, New Amsterdam Pharma, Novartis, Resverlogix, and Sanofi Regeneron; consulting fees from Akcea Therapeutics, Amgen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly and Company, Esperion Therapeutics, Kowa, Merck, Novo Nordisk, Pfizer, Sanofi Regeneron, Takeda, Vaxxinity, Silence Therapeutics, and CSL Sequiris; is a named inventor on a patent planned, issued or pending with Amgen; and is President of Cardiac Society of Australia and New Zealand. DLB reports grants or contracts from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, Cincor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Eli Lilly and Company, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer Inc, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89bio, Otsuka, and Alnylam; royalties from Elsevier; consulting fees from Broadview Ventures, Hims, and McKinsey; payment or honoraria from American College of Cardiology, Baim Institute for Clinical Research, Belvoir Publications, Boston Scientific, Cleveland Clinic, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, Novartis, Population Health Research Institute, Rutgers University, Canadian Medical and Surgical Knowledge Translation Research Group, Cowen and Company, HMP Global, Journal of the American College of Cardiology, K2P, Level Ex, Medtelligence/ReachMD, MJH Life Sciences, Oakstone CME, Piper Sandler, Population Health Research Institute, Slack Publications, WebMD, Wiley, Society of Cardiovascular Patient Care, and CSL Behring; payment for expert testimony from Arnold and Porter law firm; meeting/travel support from American College of Cardiology, Society of Cardiovascular Patient Care, and American Heart Association; a pending patent for Sotagliflozin; participation on data monitoring or advisory boards for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, AngioWave, Baim Institute, Bayer, Boehringer Ingelheim, Boston Scientific, Cardax, CellProthera, Cereno Scientific, Cleveland Clinic, Contego Medical, Duke Clinical Research Institute, Elsevier Practice Update Cardiology, Janssen, Level Ex, Mayo Clinic, Medscape Cardiology, Merck, Mount Sinai School of Medicine, MyoKardia, NirvaMed, Novartis, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Population Health Research Institute, and Stasys; leadership or fiduciary roles with American College of Cardiology, AngioWave, Boston VA Research Institute, Bristol Myers Squibb, DRS.LINQ, High Enroll, Society of Cardiovascular Patient Care, TobeSoft, and AHA NYC Chapter; stock or stock options in AngioWave, Bristol Myers Squibb, DRS.LINQ, and High Enroll; and other financial or non-financial interests in Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), American Heart Association Quality Oversight Committee (Chair), VA CART Research and Publications Committee (Chair), Contego Medical (Chair, PERFORMANCE 2), conducts unfunded research with FlowCo and Takeda, and is site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Phillips SpectraWAVE, Svelte, and Vascular Solutions. JBB reports grant support from Dexcom, Insulet, MannKind, NovaTarg, Novo Nordisk, Sanofi, Tolerion, and vTv Therapeutics; consulting fees from Novo Nordisk, Alkahest, Altimmune, Anji, AstraZeneca, Bayer, Biomea Fusion Inc, Boehringer Ingelheim, CeQur, Cirius Therapeutics Inc, Corcept Therapeutics, CultHealth, Eli Lilly and Company, embecta, GentiBio, Glycadia, Glyscend, Janssen, Mellitus Health, Metsera, Moderna, Pendulum Therapeutics, Praetego, Sanofi, Stability Health, Tandem, Terns Inc, Valo, and Zealand Pharma; payment for expert testimony from Medtronic; participation on data monitoring or advisory boards for Alkahest, Altimmune, AstraZeneca, and Tandem; a leadership or fiduciary role with Association of Clinical and Translational Science; stock or stock options in Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio, Praetego and Stability Health; and other financial or other non-financial interests in Dasman Diabetes Center, Kuwait City (scientific advisory board), and ReachMD and Mediflix (audiovisual content development). SDP reports consultation for Abbott, Amarin, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Hengrui Pharmaceuticals, Menarini International, MSD, Novo Nordisk, and Sanofi; grant support from AstraZeneca and Boehringer Ingelheim; and speaker fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Laboratori Guidotti, MSD, Novartis, Novo Nordisk, and Sanofi.. SEK reports consulting fees from Anji Pharamceuticals, Eli Lilly and Company, Merck, and Novo Nordisk; and payment or honoraria from Novo Nordisk. AML reports grants or contracts from Eli Lilly and Company; consulting fees from Eli Lilly and Company, Novo Nordisk, and Novartis; and meeting/travel support from Novo Nordisk and Eli Lilly and Company. DKM reports research support for clinical trials leadership from Boehringer Ingelheim, Merck & Co, Pfizer, AstraZeneca, Novo Nordisk, Esperion, Lilly USA, Lexicon, CSL Behring, and New Amsterdam; and honoraria for consultancy from Lilly USA, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Applied Therapeutics, Altimmune, CSL Behring, Bayer, and Intercept. MAN reports grants or contracts from Merck, Sharp & Dohme; consulting fees from Boehringer Ingelheim, Berlin-Chemie/Menarini, Eli Lilly and Company, Medtronic, Merck, Sharp & Dohme, Novo Nordisk, Pfizer, Regor, Structure Therapeutics (Gasherbrum), and Sun Pharma; payment or honoraria from Berlin-Chemie/Menarini, Eli Lilly and Company, Medical Learning Institute, Medscape, Merck, Sharp & Dohme, Novo Nordisk, Sanofi, and Sun Pharma; and participation on a data monitoring or advisory board with Inventiva. SEN reports that the Cleveland Clinic Center for Clinical Research has received funding to perform clinical trials from Abbvie, AstraZeneca, Arrowhead, Amgen, Bristol Myers Squibb, Eli Lilly, Medtronic, MyoKardia, New Amsterdam Pharmaceuticals, Novartis, and Silence Therapeutics. NS reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, and Novartis; a grant from Roche Diagnostics; and personal fees from Abbott Laboratories, Amgen, Eli Lilly and Company, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi. BZ reports consulting fees from Eli Lilly and Company. SZ reports grants or contracts from NHMRC, Australian Government Department of Health and Aged Care, JDRF Centre of Excellence, and MRFF; consulting fees from Eli Lilly Australia, Boehringer-Ingelheim, MSD Australia, Astra Zeneca, Novo Nordisk, and Sanofi; payment or honoraria from Heart Foundation; meeting/travel support from Australian Diabetes Society 2022, International Diabetes Federation 2022, and KDIGO Implementation Summit on Diabetes Management in CKD; and leadership or fiduciary roles with Melanoma and Skin Cancer Trials Ltd., Australian Clinical Trials Alliance, and Victorian Institute of Forensic Medicine. JB reports consulting fees from Eli Lilly and Company, ReCor, and Medtronic; and participation on advisory boards for ReCor, Medtronic, and Eli Lilly and Company. AB, DM, HN, IP, GW, and RJW are employees and shareholders in Eli Lilly and Company. DD reports consulting fees from Eli Lilly and Company, Sun Pharmaceuticals, and Structure Therapeutics; payment or honoraria from University of Chicago, University of Iowa, and Korean Diabetes Association; meeting/travel support from American Diabetes Association; and stock or stock options in MBX Biosciences.
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