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Cardiovascular & Hematological Disorders-Drug Targets

Cardiovascular & Hematological Disorders-Drug Targets

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ISSN (Print): 1871-529X
ISSN (Online): 2212-4063

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Perspective

Oral Semaglutide: A Step Forward in Cardiovascular Risk Management for Type 2 Diabetes

Author(s): Eder Luna-Ceron*orcid of author, Lakshmi Kattamuri, Sparsha Reddy Duvvuru and Debabrata Mukherjee

Volume 25, Issue 4, 2025

Published on: 11 August, 2025

Page: [227 - 230] Pages: 4

DOI: 10.2174/011871529X421551250801194823

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Abstract

Recent cardiovascular outcome trials (CVOTs) have reshaped the therapeutic landscape of type 2 diabetes mellitus (T2DM), revealing that certain glucose-lowering agents, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), offer substantial cardiovascular benefits beyond glycemic control. Injectable GLP-1RAs, such as semaglutide and liraglutide, have been shown to reduce major adverse cardiovascular events (MACE), but barriers, including cost, access, and the burden of injections, persist. The SOUL trial marks a significant milestone by evaluating oral semaglutide in high-risk patients, demonstrating a 14% reduction in MACE versus placebo and reinforcing GLP-1RAs cardioprotective potential in an oral formulation. This advancement holds promise for patient populations underrepresented in prior trials. However, gastrointestinal side effects and strict dosing requirements challenge long-term adherence. While the findings suggest improved accessibility and real-world applicability, further comparative trials with injectables, extended follow-up, and cost-effectiveness studies are essential. As evidence evolves, oral GLP-1RAs may represent a more patient-centered approach to managing diabetes and cardiovascular risk. This perspective article aims to explore the implications of the SOUL trial, highlight ongoing challenges in adherence and implementation, and discuss the future role of oral GLP-1RAs in cardiovascular and diabetes care.

Keywords: Oral semaglutide, GLP-1 receptor agonists, cardiovascular outcomes, type 2 diabetes, SOUL trial, medication adherence.

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[1]
Ferrannini, E.; DeFronzo, R.A. Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes. Eur. Heart J., 2015, 36(34), 2288-2296.
[http://dx.doi.org/10.1093/eurheartj/ehv239] [PMID: 26063450]
[2]
Mares, A.C.; Chatterjee, S.; Mukherjee, D. Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. Curr. Opin. Cardiol., 2022, 37(4), 350-355.
[http://dx.doi.org/10.1097/HCO.0000000000000955] [PMID: 35175229]
[3]
Rivera, F.B.; Cruz, L.L.A.; Magalong, J.V.; Ruyeras, J.M.M.J.; Aparece, J.P.; Bantayan, N.R.B.; Lara-Breitinger, K.; Gulati, M. Cardiovascular and renal outcomes of glucagon-like peptide 1 receptor agonists among patients with and without type 2 diabetes mellitus: A meta-analysis of randomized placebo-controlled trials. Am J. Prev Cardiol., 2024, 18, 100679.
[http://dx.doi.org/10.1016/j.ajpc.2024.100679] [PMID: 38779187]
[4]
Zheng, Z.; Zong, Y.; Ma, Y.; Tian, Y.; Pang, Y.; Zhang, C.; Gao, J. Glucagon-like peptide-1 receptor: Mechanisms and advances in therapy. Signal Transduct. Target. Ther., 2024, 9(1), 234.
[http://dx.doi.org/10.1038/s41392-024-01931-z] [PMID: 39289339]
[5]
Waldrop, S.W.; Johnson, V.R.; Stanford, F.C. Inequalities in the provision of GLP-1 receptor agonists for the treatment of obesity. Nat. Med., 2024, 30(1), 22-25.
[http://dx.doi.org/10.1038/s41591-023-02669-x] [PMID: 38172631]
[6]
McGuire, D.K.; Marx, N.; Mulvagh, S.L.; Deanfield, J.E.; Inzucchi, S.E.; Pop-Busui, R.; Mann, J.F.E.; Emerson, S.S.; Poulter, N.R.; Engelmann, M.D.M.; Ripa, M.S.; Hovingh, G.K.; Brown-Frandsen, K.; Bain, S.C.; Cavender, M.A.; Gislum, M.; David, J.P.; Buse, J.B. Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes. N. Engl. J. Med., 2025, 392(20), 2001-2012.
[http://dx.doi.org/10.1056/NEJMoa2501006] [PMID: 40162642]
[7]
Husain, M.; Birkenfeld, A.L.; Donsmark, M.; Dungan, K.; Eliaschewitz, F.G.; Franco, D.R.; Jeppesen, O.K.; Lingvay, I.; Mosenzon, O.; Pedersen, S.D.; Tack, C.J.; Thomsen, M.; Vilsbøll, T.; Warren, M.L.; Bain, S.C. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med., 2019, 381(9), 841-851.
[http://dx.doi.org/10.1056/NEJMoa1901118] [PMID: 31185157]
[8]
Joseph, J.J.; Deedwania, P.; Acharya, T.; Aguilar, D.; Bhatt, D.L.; Chyun, D.A.; Di Palo, K.E.; Golden, S.H.; Sperling, L.S. Comprehensive management of cardiovascular risk factors for adults with type 2 diabetes: A scientific statement from the American Heart Association. Circulation, 2022, 145(9), e722-e759.
[http://dx.doi.org/10.1161/CIR.0000000000001040] [PMID: 35000404]
[9]
Marso, S.P.; Bain, S.C.; Consoli, A.; Eliaschewitz, F.G.; Jódar, E.; Leiter, L.A.; Lingvay, I.; Rosenstock, J.; Seufert, J.; Warren, M.L.; Woo, V.; Hansen, O.; Holst, A.G.; Pettersson, J.; Vilsbøll, T. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med., 2016, 375(19), 1834-1844.
[http://dx.doi.org/10.1056/NEJMoa1607141] [PMID: 27633186]
[10]
Spain, C.V.; Wright, J.J.; Hahn, R.M.; Wivel, A.; Martin, A.A. Self-reported barriers to adherence and persistence to treatment with injectable medications for type 2 diabetes. Clin. Ther., 2016, 38(7), 1653-1664.e1.
[http://dx.doi.org/10.1016/j.clinthera.2016.05.009] [PMID: 27364806]

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