A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes

Summary

The researchers are doing this study to look whether the type 2 diabetes medicine, semaglutide, has a positive effect on heart disease. Participants will either get semaglutide tablets or placebo tablets ("dummy" medicine) - which treatment is decided by chance. Participants must take one tablet with water every morning on an empty stomach and not eat or drink anything for at least 30 minutes. The study will last for about 3.5-5 years. Participants will have up to 25 clinic visits and 1 phone call with the study doctor. Women cannot be in the study if pregnant, breast-feeding or if they plan to become pregnant during the study period.

Timeline

Start

2019-06-17

Primary completion

2024-08-23

Completion

2024-08-23

Publications

• Mulvagh SL, Inzucchi SE, Marx N, Poulter NR, Deanfield JE, Pop-Busui R, Emerson SS, Mann JFE, Engelmann MDM, Hovingh GK, Mandavya K, Davicevic-Elez Z, Jeppesen OK, Lorenzatti A, Oguz A, Mankovsky B, Deerochanawong C, Gorgojo-Martinez JJ, Ji L, Bain SC, McGuire DK, Buse JB; SOUL Study Group. Oral Semaglutide and Change in Cardiovascular Risk Factors in High-Risk Type 2 Diabetes: A Post Hoc Secondary Analysis of the SOUL Randomized Clinical Trial. JAMA Cardiol. 2026 May 1;11(5):427-437. doi: 10.1001/jamacardio.2026.0245.
• Pop-Busui R, Rasmussen S, Deanfield JE, Buse JB, Marx N, Mulvagh SL, Inzucchi SE, Mann JFE, Emerson SS, Poulter NR, Engelmann MDM, Hovingh GK, Bayer Tanggaard K, Birkenfeld AL, Connelly KA, Haluzik M, Cavender MA, Kellerer M, Jhund PS, Gregersen S, Nielsen OW, Lam CSP, McGuire DK; SOUL Study Group. Oral Semaglutide and Heart Failure Outcomes in Persons With Type 2 Diabetes: A Secondary Analysis of the SOUL Randomized Clinical Trial. JAMA Intern Med. 2026 Apr 1;186(4):426-436. doi: 10.1001/jamainternmed.2025.7774.
• Mann JFE, Marx N, Deanfield JE, Emerson SS, Inzucchi SE, McGuire DK, Mulvagh SL, Pop-Busui R, Poulter NR, Engelmann MDM, Hovingh GK, Belmar N, Idorn T, Jeppesen OK, Birkenfeld AL, Amod A, Mankovsky B, Desouza C, Gorgojo-Martinez JJ, Arechavaleta R, Tu ST, Buse JB; SOUL Study Group*. Impact of Oral Semaglutide on Kidney Outcomes in People With Type 2 Diabetes: Results From the SOUL Randomized Trial. Diabetes Care. 2026 Feb 1;49(2):257-265. doi: 10.2337/dc25-1080.
• Borlaug BA, Holse C, Jung MH, Lincoff AM, Mulvagh SL, Staerk-Ostergaard J, Tuttle KR, Petrie MC. Prevalence and Associations of Systemic Inflammation in Heart Failure Across the Spectrum of Ejection Fraction. JACC Heart Fail. 2026 Feb;14(2):102712. doi: 10.1016/j.jchf.2025.102712. Epub 2025 Oct 16.
• McGuire DK, Marx N, Mulvagh SL, Deanfield JE, Inzucchi SE, Pop-Busui R, Mann JFE, Emerson SS, Poulter NR, Engelmann MDM, Ripa MS, Hovingh GK, Brown-Frandsen K, Bain SC, Cavender MA, Gislum M, David JP, Buse JB; SOUL Study Group. Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes. N Engl J Med. 2025 May 29;392(20):2001-2012. doi: 10.1056/NEJMoa2501006. Epub 2025 Mar 29.
• Marx N, Deanfield JE, Mann JFE, Arechavaleta R, Bain SC, Bajaj HS, Bayer Tanggaard K, Birkenfeld AL, Buse JB, Davicevic-Elez Z, Desouza C, Emerson SS, Engelmann MDM, Hovingh GK, Inzucchi SE, Jhund PS, Mulvagh SL, Pop-Busui R, Poulter NR, Rasmussen S, Tu ST, McGuire DK; SOUL Study Group. Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial. Circulation. 2025 Jun 10;151(23):1639-1650. doi: 10.1161/CIRCULATIONAHA.125.074545. Epub 2025 Mar 29.
• Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.

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