Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes

Summary

This trial is conducted globally. The aim of the trial is to evaluate cardiovascular and other long-term outcomes with semaglutide in subjects with type 2 diabetes. The trial is event-driven, i.e. the maximum trial duration (up to max. 148 weeks) will depend on the accrual of major adverse cardiovascular events (MACE) in this trial and the remaining research programme. The incidence of MACE will be monitored throughout the trial which will be terminated according to plan when pre-specified stopping criteria are met.

Timeline

Start

2013-02-21

Primary completion

2016-03-15

Completion

2016-03-15

Publications

• Background Verma S, Bain SC, Monk Fries T, Mazer CD, Nauck MA, Pratley RE, Rasmussen S, Saevereid HA, Zinman B, Buse JB. Duration of diabetes and cardiorenal efficacy of liraglutide and semaglutide: A post hoc analysis of the LEADER and SUSTAIN 6 clinical trials. Diabetes Obes Metab. 2019 Jul;21(7):1745-1751. doi: 10.1111/dom.13698. Epub 2019 Apr 2.
• Results Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15.
• Results Vilsboll T, Bain SC, Leiter LA, Lingvay I, Matthews D, Simo R, Helmark IC, Wijayasinghe N, Larsen M. Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. Diabetes Obes Metab. 2018 Apr;20(4):889-897. doi: 10.1111/dom.13172. Epub 2018 Jan 8.
• Results Carlsson Petri KC, Ingwersen SH, Flint A, Zacho J, Overgaard RV. Semaglutide s.c. Once-Weekly in Type 2 Diabetes: A Population Pharmacokinetic Analysis. Diabetes Ther. 2018 Aug;9(4):1533-1547. doi: 10.1007/s13300-018-0458-5. Epub 2018 Jun 15.
• Results Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jodar E, Mehta R, Woo V, Lingvay I. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Diabetes Metab. 2019 Oct;45(5):409-418. doi: 10.1016/j.diabet.2018.12.001. Epub 2019 Jan 4.
• Results Leiter LA, Bain SC, Hramiak I, Jodar E, Madsbad S, Gondolf T, Hansen T, Holst I, Lingvay I. Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial. Cardiovasc Diabetol. 2019 Jun 6;18(1):73. doi: 10.1186/s12933-019-0871-8.
• 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.
• Bain SC, Belmar N, Hoff ST, Husain M, Rasmussen S, Vilsboll T, Petrie MC. Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN 6 and PIONEER 6. Diabetes Ther. 2025 Jan;16(1):15-28. doi: 10.1007/s13300-024-01659-7. Epub 2024 Nov 9.
• Rossing P, Bain SC, Bosch-Traberg H, Sokareva E, Heerspink HJL, Rasmussen S, Mellbin LG. Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis. Cardiovasc Diabetol. 2023 Aug 24;22(1):220. doi: 10.1186/s12933-023-01949-7.
• Strain WD, Frenkel O, James MA, Leiter LA, Rasmussen S, Rothwell PM, Sejersten Ripa M, Truelsen TC, Husain M. Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes: Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6. Stroke. 2022 Sep;53(9):2749-2757. doi: 10.1161/STROKEAHA.121.037775. Epub 2022 May 18.
• Husain M, Consoli A, De Remigis A, Pettersson Meyer AS, Rasmussen S, Bain S. Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6. Cardiovasc Diabetol. 2022 Apr 28;21(1):64. doi: 10.1186/s12933-022-01489-6.
• Verma S, Al-Omran M, Leiter LA, Mazer CD, Rasmussen S, Saevereid HA, Sejersten Ripa M, Bonaca MP. Cardiovascular efficacy of liraglutide and semaglutide in individuals with diabetes and peripheral artery disease. Diabetes Obes Metab. 2022 Jul;24(7):1288-1299. doi: 10.1111/dom.14700. Epub 2022 Apr 11.
• Verma S, Fainberg U, Husain M, Rasmussen S, Ryden L, Ripa MS, Buse JB. Applying REWIND cardiovascular disease criteria to SUSTAIN 6 and PIONEER 6: An exploratory analysis of cardiovascular outcomes with semaglutide. Diabetes Obes Metab. 2021 Jul;23(7):1677-1680. doi: 10.1111/dom.14360. Epub 2021 Mar 18.
• Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4.
• Verma S, McGuire DK, Bain SC, Bhatt DL, Leiter LA, Mazer CD, Monk Fries T, Pratley RE, Rasmussen S, Vrazic H, Zinman B, Buse JB. Effects of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across body mass index categories in type 2 diabetes: Results of the LEADER and SUSTAIN 6 trials. Diabetes Obes Metab. 2020 Dec;22(12):2487-2492. doi: 10.1111/dom.14160. Epub 2020 Sep 4.
• Verma S, Bain SC, Honore JB, F E Mann J, A Nauck M, E Pratley R, Rasmussen S, Sejersten Ripa M, Zinman B, Buse JB. Impact of microvascular disease on cardiovascular outcomes in type 2 diabetes: Results from the LEADER and SUSTAIN 6 clinical trials. Diabetes Obes Metab. 2020 Nov;22(11):2193-2198. doi: 10.1111/dom.14140. Epub 2020 Aug 12.
• Leiter LA, Bain SC, Bhatt DL, Buse JB, Mazer CD, Pratley RE, Rasmussen S, Ripa MS, Vrazic H, Verma S. The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials. Diabetes Obes Metab. 2020 Sep;22(9):1690-1695. doi: 10.1111/dom.14079. Epub 2020 Jun 3.
• Jodar E, Michelsen M, Polonsky W, Rea R, Sandberg A, Vilsboll T, Warren M, Harring S, Ziegler U, Bain S. Semaglutide improves health-related quality of life versus placebo when added to standard of care in patients with type 2 diabetes at high cardiovascular risk (SUSTAIN 6). Diabetes Obes Metab. 2020 Aug;22(8):1339-1347. doi: 10.1111/dom.14039. Epub 2020 Apr 27.
• Husain M, Bain SC, Jeppesen OK, Lingvay I, Sorrig R, Treppendahl MB, Vilsboll T. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5.
• DeSouza C, Cariou B, Garg S, Lausvig N, Navarria A, Fonseca V. Efficacy and Safety of Semaglutide for Type 2 Diabetes by Race and Ethnicity: A Post Hoc Analysis of the SUSTAIN Trials. J Clin Endocrinol Metab. 2020 Feb 1;105(2):dgz072. doi: 10.1210/clinem/dgz072.
• Wittbrodt ET, Eudicone JM, Bell KF, Enhoffer DM, Latham K, Green JB. Generalizability of glucagon-like peptide-1 receptor agonist cardiovascular outcome trials enrollment criteria to the US type 2 diabetes population. Am J Manag Care. 2018 Apr;24(8 Suppl):S146-S155.

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