Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity

Summary

The researchers are doing the study to see if semaglutide may reduce the risk of having cardiovascular events in patients with overweight or obesity and with prior cardiovascular disease. The participant will either get semaglutide (active medicine) or placebo ("dummy" medicine). Which treatment the participants get is decided by chance. The participant's chance of getting semaglutide or placebo is the same. The participant will get the study medicine in a pen. The participants will need to use the pen to inject the study medicine in a skinfold once a week. The study will last for about 2.5 to 5 years. Participants will have up to 25 clinic visits with the study doctor.

Timeline

Start

2018-10-24

Primary completion

2023-06-21

Completion

2023-06-29

Publications

• Results Ryan DH, Lingvay I, Colhoun HM, Deanfield J, Emerson SS, Kahn SE, Kushner RF, Marso S, Plutzky J, Brown-Frandsen K, Gronning MOL, Hovingh GK, Holst AG, Ravn H, Lincoff AM. Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design. Am Heart J. 2020 Nov;229:61-69. doi: 10.1016/j.ahj.2020.07.008. Epub 2020 Jul 17.
• Results Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.
• Results Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornoe CW, Ryan DH; SELECT Trial Investigators. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. Epub 2023 Nov 11.
• Meyhofer SM, Cariou B, Cercato C, Colhoun HM, Deanfield J, Long MT, Jeppesen OK, Lincoff AM, Lingvay I, Plutzky J, Newsome PN, Nicholls SJ, Quiroga M, Santini F, Sanyal AJ, Kahn SE; SELECT Trial Investigators. Semaglutide on liver fibrosis and heart outcomes in patients at high risk of liver fibrosis: a prespecified analysis of the SELECT randomized trial. Nat Med. 2026 May;32(5):1686-1693. doi: 10.1038/s41591-026-04281-1. Epub 2026 Apr 2.
• Nicholls SJ, Ryan DH, Deanfield J, Ferreira D, Lang CC, Lincoff AM, Lingvay I, Lubker C, Terns PP, Rasmussen S, Stensen S, Weeke PE, Kahn SE; SELECT Trial Investigators. Semaglutide and Hospitalizations in Patients With Obesity and Established Cardiovascular Disease: An Exploratory Analysis of the SELECT Randomized Clinical Trial. JAMA Cardiol. 2026 Feb 1;11(2):156-164. doi: 10.1001/jamacardio.2025.4824.
• Deanfield J, Lincoff AM, Kahn SE, Emerson SS, Lingvay I, Scirica BM, Plutzky J, Kushner RF, Colhoun HM, Hovingh GK, Stensen S, Weeke PE, Jeppesen OK, Bravo R, Wu CC, Komuro I, Santini F, Hjelmesaeth J, Urina-Triana M, Buscemi S, Ryan DH. Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial. Lancet. 2025 Nov 8;406(10516):2257-2268. doi: 10.1016/S0140-6736(25)01375-3. Epub 2025 Oct 22.
• Lubker C, Bhavsar J, Duque do Vale R, Emerson SS, Nortoft E, Plutzky J, Roberts G, Tarp JM, Lincoff AM. The Composite Number Needed to Treat for Semaglutide in Populations with Overweight or Obesity and Established Cardiovascular Disease Without Diabetes. Adv Ther. 2025 May;42(5):2513-2525. doi: 10.1007/s12325-025-03176-w. Epub 2025 Mar 29.
• McEwan P, Bog M, Faurby M, Foos V, Lingvay I, Lubker C, Miller R, Toliver JC, Yeates F, Lincoff AM. Cost-effectiveness of semaglutide in people with obesity and cardiovascular disease without diabetes. J Med Econ. 2025 Dec;28(1):268-278. doi: 10.1080/13696998.2025.2459529. Epub 2025 Feb 12.
• Badve SV, Bilal A, Lee MMY, Sattar N, Gerstein HC, Ruff CT, McMurray JJV, Rossing P, Bakris G, Mahaffey KW, Mann JFE, Colhoun HM, Tuttle KR, Pratley RE, Perkovic V. Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2025 Jan;13(1):15-28. doi: 10.1016/S2213-8587(24)00271-7. Epub 2024 Nov 25.
• Mendonca L, Moura H, Chaves PC, Neves JS, Ferreira JP. The Impact of Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes: A Meta-Analysis of Randomized Placebo-Controlled Trials. Clin J Am Soc Nephrol. 2025 Feb 1;20(2):159-168. doi: 10.2215/CJN.0000000584. Epub 2024 Oct 8.
• Kosiborod MN, Deanfield J, Pratley R, Borlaug BA, Butler J, Davies MJ, Emerson SS, Kahn SE, Kitzman DW, Lingvay I, Mahaffey KW, Petrie MC, Plutzky J, Rasmussen S, Ronnback C, Shah SJ, Verma S, Weeke PE, Lincoff AM; SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM Trial Committees and Investigators. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet. 2024 Sep 7;404(10456):949-961. doi: 10.1016/S0140-6736(24)01643-X. Epub 2024 Aug 30.
• Scirica BM, Lincoff AM, Lingvay I, Bogdanski P, Buscemi S, Colhoun H, Craciun AE, Ezhov M, Hardt-Lindberg S, Kleist Jeppesen O, Matos ALSA, Node K, Schiele F, Toplak H, van Beek A, Weeke PE, Wiviott SD, Deanfield J, Ryan D. The Effect of Semaglutide on Mortality and COVID-19-Related Deaths: An Analysis From the SELECT Trial. J Am Coll Cardiol. 2024 Oct 22;84(17):1632-1642. doi: 10.1016/j.jacc.2024.08.007. Epub 2024 Aug 30.
• Deanfield J, Verma S, Scirica BM, Kahn SE, Emerson SS, Ryan D, Lingvay I, Colhoun HM, Plutzky J, Kosiborod MN, Hovingh GK, Hardt-Lindberg S, Frenkel O, Weeke PE, Rasmussen S, Goudev A, Lang CC, Urina-Triana M, Pietila M, Lincoff AM; SELECT Trial Investigators. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. Lancet. 2024 Aug 24;404(10454):773-786. doi: 10.1016/S0140-6736(24)01498-3.
• Colhoun HM, Lingvay I, Brown PM, Deanfield J, Brown-Frandsen K, Kahn SE, Plutzky J, Node K, Parkhomenko A, Ryden L, Wilding JPH, Mann JFE, Tuttle KR, Idorn T, Rathor N, Lincoff AM. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial. Nat Med. 2024 Jul;30(7):2058-2066. doi: 10.1038/s41591-024-03015-5. Epub 2024 May 25.
• Ryan DH, Lingvay I, Deanfield J, Kahn SE, Barros E, Burguera B, Colhoun HM, Cercato C, Dicker D, Horn DB, Hovingh GK, Jeppesen OK, Kokkinos A, Lincoff AM, Meyhofer SM, Oral TK, Plutzky J, van Beek AP, Wilding JPH, Kushner RF. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med. 2024 Jul;30(7):2049-2057. doi: 10.1038/s41591-024-02996-7. Epub 2024 May 13.
• Rowe IA, Allen AM. Hepatic steatosis provides the terroir that promotes the development of cardiovascular risk factors and disease. Hepatology. 2023 Jun 1;77(6):1843-1845. doi: 10.1097/HEP.0000000000000327. Epub 2023 Feb 6. No abstract available.
• Leite AR, Angelico-Goncalves A, Vasques-Novoa F, Borges-Canha M, Leite-Moreira A, Neves JS, Ferreira JP. Effect of glucagon-like peptide-1 receptor agonists on cardiovascular events in overweight or obese adults without diabetes: A meta-analysis of placebo-controlled randomized trials. Diabetes Obes Metab. 2022 Aug;24(8):1676-1680. doi: 10.1111/dom.14707. Epub 2022 May 3.
• Mares AC, Chatterjee S, Mukherjee D. Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. Curr Opin Cardiol. 2022 Jul 1;37(4):350-355. doi: 10.1097/HCO.0000000000000955. Epub 2022 Feb 16.
• Kanie T, Mizuno A, Takaoka Y, Suzuki T, Yoneoka D, Nishikawa Y, Tam WWS, Morze J, Rynkiewicz A, Xin Y, Wu O, Providencia R, Kwong JS. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev. 2021 Oct 25;10(10):CD013650. doi: 10.1002/14651858.CD013650.pub2.

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