Cardiovascular effects of GLP-1 receptor agonists in patients with type 2 diabetes mellitus
Keywords:
AGONISTAS RECEPTOR DE PÉPTIDOS SIMILARES AL GLUCAGÓN; DIABETES MELLITUS TIPO 2; ENFERMEDADES CARDIOVASCULARES; SALUD CARDIOVASCULAR., GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS; DIABETES MELLITUS, TYPE 2; CARDIOVASCULAR DISEASES; CARDIOVASCULAR HEALTH., AGONISTAS DO RECEPTOR DE PEPTÍDEOS SEMELHANTES AO GLUCAGON; DIABETES MELLITUS TIPO 2; DOENÇAS CARDIOVASCULARES; SAÚDE CARDIOVASCULAR.Abstract
Introduction: type 2 diabetes mellitus is associated with high cardiovascular morbidity and mortality, which drives the search for therapies that go beyond traditional glycemic control.
Objective: to evaluate the scientific evidence on the cardiovascular effects of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus.
Methods: a systematic review of the scientific literature was conducted across multiple databases. The search was performed using an algorithm with keywords and Boolean operators to identify relevant sources. After applying predefined inclusion and exclusion criteria, the selected studies were critically analyzed in terms of currency, methodological quality, and thematic relevance, and subsequently integrated into the final synthesis of the review.
Development: the findings show that glucagon-like peptide-1 receptor agonists reduce major adverse cardiovascular events, cardiovascular mortality, and hospitalizations for heart failure. Liraglutide and semaglutide stand out for their significant benefits, while other agents exhibit variable effects. Pleiotropic mechanisms were identified, including improvement of endothelial function, reduction of oxidative stress, and protection of cardiomyocytes. However, efficacy varies according to the specific drug and the population studied, highlighting the need for individualized therapy.
Conclusions: glucagon-like peptide-1 receptor agonists represent a promising strategy for patients with type 2 diabetes and high cardiovascular risk. Although some agents demonstrate consistent benefits, the heterogeneity of outcomes underscores the need for further comparative studies and a personalized approach that integrates metabolic control with cardiovascular protection.
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References
1. Organización Panamericana de la Salud. Diabetes. Washington, D.C.: OPS [Internet]; 2024. [citado 16/07/2024]. Disponible en: https://www.paho.org/es/temas/diabetes#:~:text=La%20diabetes%20tipo%202%20(antes,diabetes%20tienen%20diabetes%20tipo%202
2. Astudillo Machuca AC. Efectividad de los agonistas del receptor GLP-1 como tratamiento en pacientes con Diabetes mellitus tipo 2. Universidad Católica de Cuenca [Internet]. 2023 [citado 16/07/2024]. Disponible en: https://dspace.ucacue.edu.ec/handle/ucacue/14827
3. Silva AB, Souza AH, Santos MC, et al. Mechanisms of Insulin Resistance in Type 2 Diabetes Mellitus. J Mol Sci [Internet]. 2020 [citado 16/07/2024];21(17):6275. https://doi.org/10.3390/ijms21176275
4. Mosquera N, Vergara E, Camacho PA. Factores de riesgo cardiovascular en pacientes con diabetes mellitus tipo 2. Rev Cienc Salud [Internet]. 2020 [citado 16/07/2024];2(1):44-55. Disponible en: http://www.scielo.org.co/scielo.php?pid=S2500-50062020000100044&script=sci_arttext#
5. Patel, A, MacMahon, S, Chalmers, J, Neal, B, Billot, L, Woodward, M, Marre, M, Cooper, M, Glasziou, P, Grobbee, D, et al. Grupo de colaboración ADVANCE. Grupo de colaboración ADVANCE. Control intensivo de la glucemia y resultados vasculares en pacientes con diabetes tipo 2. N Engl J Med [Internet]. 2020 [citado 16/07/2024]; 358: 2560–2572. Disponible en: https://pubmed.ncbi.nlm.nih.gov/18539916/
6. Singh AK, Gupta R, Ghosh A, Misra A. Diabetes in COVID-19: prevalence, pathophysiology, prognosis and practical considera-tions. Diabetes Metab Syndr14: 303–310 [Internet]. 2020 [citado 16/07/2024];14(4) Disponible en: https://pubmed.ncbi.nlm.nih.gov/32298981/
7. Bailey, CJ, Marx, N. Protección cardiovascular en la diabetes tipo 2: perspectivas de ensayos de resultados recientes. Diabetes Obes Metab [Internet]. 2019 [citado 16/07/2024];21:3–14. Disponible en: https://pubmed.ncbi.nlm.nih.gov/30091169/
8. Casas Figueroa LA. Analogos de GLP1: marcando nuevas rutas en el manejo de la diabetes. Rev Colomb Endocrinol Diabetes Metab [Internet]. 2022 [citado 16/07/2024];9(2):144–6. Disponible en: https://revistaendocrino.org/index.php/rcedm/article/view/754
9. Rowlands J, Heng J, Newsholme P, et al. Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function. Front Endocrinol (Lausanne) [Internet]. 2019 [citado 16/07/2024]; 9: 672.Disponible en: https://pmc.ncbi.nlm.nih.gov/articles/PMC6266510/
10. American Diabetes Association. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2019. Diabetes Care [Internet]. 2019 [citado 16/07/2024]; 42(Suppl. 1): S90–S102. Disponible en: https://pubmed.ncbi.nlm.nih.gov/30559235/
11. Dave, CV, Schneeweiss, S, Wexler, DJ, Brill, G, Patorno, E. Tendencias en las características clínicas y preferencias de prescripción de inhibidores de SGLT2 y agonistas del receptor GLP-1, 2013-2018. Diabetes Care [Internet]. 2020 [citado 16/07/2024]; 43:921–924. Disponible en: https://pubmed.ncbi.nlm.nih.gov/32041899/
12. Nauck, MA, Quast, DR, Wefers, J, Meier, JJ. Agonistas del receptor de GLP-1 en el tratamiento de la diabetes tipo 2: estado del arte. Mol Metab [Internet]. 2021 [citado 16/07/2024]; 46:101102. Disponible en: https://pubmed.ncbi.nlm.nih.gov/33068776/
13. Nauck, MA, Meier, JJ, Cavender, MA, Abd El Aziz, M, Drucker, DJ. Acciones cardiovasculares y resultados clínicos con agonistas del receptor del péptido similar al glucagón-1 e inhibidores de la dipeptidil peptidasa-4. Circulation [Internet]. 2019 [citado 16/07/2024]; 136: 849–870. Disponible en: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.117.028136
14. Tomas E, Stanojevic V, Habener JF. El nonapéptido derivado de GLP-1 GLP-1(28- 36)amida se dirige a las mitocondrias y suprime la producción de glucosa y el estrés oxidativo en hepatocitos aislados de ratón. Regul Pept [Internet]. 2019[citado 16/07/2024];167(2–3):177–184. Disponible en: https://patents.google.com/patent/ES2336575T3/es
15. Shao W, et al. GLP-1(28-36) mejora la masa de células β y la eliminación de glucosa en ratones diabéticos inducidos por estreptozotocina y activa la señalización de AMPc/PKA/β-catenina en células β in vitro. Am J Physiol Endocrinol Metab [Internet]. 2019 [citado 16/07/2024]; 304(12): E1263–E1272.Disponible en: https://pubmed.ncbi.nlm.nih.gov/23571712/
16. Vargas JML, Fontalvo JER, Barrios GAC, Rincón AR, Gomez AM, Rojas SM, Bernal LI. Efecto de terapias farmacológicas para el control glicémico en pacientes con diabetes mellitus tipo 2 en los desenlaces vasculares. Rev. Colomb. Nefrol [Internet]. 2020[citado 16/07/2024]; 7(1). Disponible en: https://revistanefrologia.org/index.php/rcn/article/download/372/723?inline=1
17. Castillo GA, Aroca G, Buelvas J, Buitrago AF, Carballo V, Cárdenas JM, Gómez EA, Fériz K, Lopera JM, Melgarejo E, Restrepo K, Montejo JD, Pinzón JB, Quintero A, Rico JE, Rosero R. Recomendaciones para el manejo del riesgo cardiorrenal en el paciente con diabetes mellitus tipo 2. RCC [Internet]. 2020 [citado 16/07/2024];17(Suppl. 3).Disponible en: https://rccardiologia.com/previos/RCC%202020%20Vol.%2027/RCC_2020_27_S3/RCC_2020_27_S3_003-022.pdf
18. Heuvelman VD, Van Raalte DH, Smits MM. Cardiovascular effects of glucagon-like peptide 1 receptor agonists: from mechanistic studies in humans to clinical outcomes. Cardiovasc Res [Internet]. 2020 [citado 16/07/2024];116(5). Disponible en: https://pubmed.ncbi.nlm.nih.gov/31825468/
19. Castillo GA, Aroca G, Buelvas J, Buitrago AF, Carballo V, Cárdenas JM, Gómez EA, Fériz K, Lopera JM, Melgarejo E, Restrepo K, Montejo J, Pinzón JB, Quintero A, Rico JE, Rosero R. Recomendaciones para el manejo del riesgo cardiorrenal en el paciente con diabetes mellitus tipo 2.RCC [Internet]. 2020 [citado 16/07/2024]; 27(Suppl 3). Disponible en: https://rccardiologia.com/previos/RCC%202020%20Vol.%2027/RCC_2020_27_S3/RCC_2020_27_S3_003-022.pdf
20. Kelsey H Sheahan, Elizabeth A Wahlberg, Matthew P Gilbert.Una descripción general de los agonistas de GLP-1 y los ensayos recientes de resultados cardiovasculares. Circulation [Internet]. 2019 [citado 16/07/2024];150(22) . Disponible en: https://www.ahajournals.org/
21. Natali, A., Nesti, L., Tricò, D., & Ferrannini, E. Effects of GLP-1 receptor agonists and SGLT-2 inhibitors on cardiac structure and function: a narrative review of clinical evidence. Cardiovascular Diabetology [Internet]. 2021 [citado 16/07/2024]; 20(1). Disponible en: https://pubmed.ncbi.nlm.nih.gov/34583699/
22. American Diabetes Association. Diagnóstico de la diabetes. [Internet]. [citado 16/07/2024]. Disponible en: https://diabetes.org/espanol/diagnostico.
23. Guillaumet A, Martínez MS, Muniesa JM. Type 2 diabetes mellitus and physical activity. Nutr Hosp [Internet]. 2022 [citado 16/07/2024]; 38(2):384-391. Disponible en:
https://pubmed.ncbi.nlm.nih.gov/18803434/
24. Katsiki N, Mikhailidis DP, Banach M, et al. Lipid-lowering therapy and new-onset diabetes: is there a link? Curr Pharm Des [Internet]. 2021 [citado 16/07/2024]; 27(31): 3583-3590. Disponible en: https://link.springer.com/article/10.1007/s11883-024-01270-y https://pubmed.ncbi.nlm.nih.gov/35904915/.
25. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. Eur Heart J [Internet]. 2020 [citado 16/07/2024]; 375(4):111-121. Disponible en: https://pubmed.ncbi.nlm.nih.gov/27295427/ .
26. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med [Internet]. 2019 [citado 16/07/2024]; 373(23): 2247-2257. Disponible en: https://www.nejm.org/doi/full/10.1056/NEJMoa1509225
27. Husain M, Birkenfeld AL, Donsmark M, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. JAMA [Internet]. 2019 [citado 17/07/2024];321(1):59-69.Disponible en: https://www.nejm.org/doi/full/10.1056/NEJMoa1901118
28. Ferhatbegović L, Mršić D, Macić-Džanković A. The benefits of GLP1 receptors in cardiovascular diseases. Front Clin Diabetes Healthc [Internet].2023 [citado 17/07/2024]; 4:1293926. Disponible en: https://pubmed.ncbi.nlm.nih.gov/38143794/
29. Wang Y, Liu X, Zhang Y, et al. GLP-1 agonists and their cardiovascular benefits in type 2 diabetes. Exp Ther Med [Internet]. 2020 [citado 17/07/2024]; 20:8714. Disponible en: https://www.mdpi.com/2077-0383/14/19/6758
30. Pyke C, Heller RS, Kirk RK, Ørskov C, Reedtz-Runge S, Kaastrup P, Hvelplund A, Bardram L, Calatayud D, Knudsen LB. Cardiovascular benefits of GLP-1 agonists in type 2 diabetes. Clin Sci [Internet]. 2021 [citado 17/07/2024];132(15):1699-1712. Disponible en: https://portlandpress.com/clinsci/article-abstract/132/15/1699/71791/Cardiovascular-benefits-of-GLP-1-agonists-in-type?redirectedFrom=fulltext
31. Elbert A, Castellaro C, Litwak L, Inserra F, Wassermann A, Sinay I. Efectos renales de los agonistas GLP-1 en la diabetes tipo 2. Medicina (B Aires) [Internet]. 2022[citado 17/07/2024]; 82(4):576–90. Disponible en: https://www.medicinabuenosaires.com/PMID/35904915.pdf
32. Cases A. Agonistas del receptor de péptido similar al glucagón tipo 1 (GLP-1) en el manejo del paciente con diabetes mellitus tipo 2. Una aproximación para el nefrólogo. Nefrologia [Internet]. 2023 [citado 17/07/2024]; 43:399–412. Disponible en: https://www.sciencedirect.com/science/article/pii/S0211699522001266
33. Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care [Internet]. 2019 [citado 17/07/2024]; 41(12):2 669-2701. Available from: https://pubmed.ncbi.nlm.nih.gov/30291106/
34. Duran ALC, Medina MFD, Valdivieso MRA, Dunn MAE, Torres WPR, Barrera LNA, et al. Terapia incretinomimética: evidencia clínica de la eficacia de los agonistas del GLP-1R y sus efectos cardio-protectores. RLH [Internet]. 2019 [citado 17/07/2024];13(4). Disponible en: https://www.redalyc.org/journal/1702/170263336018/html/
35. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomized placebo-controlled trial. Lancet [Internet]. 2019 [citado 17/07/2024];394(10193):121-130. Available from: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00203-5/abstract
36. Sheahan KH, Wahlberg EA, Gilbert MP. Una descripción general de los agonistas de GLP-1 y los ensayos recientes de resultados cardiovasculares. Postgrad Med J. [Internet]. 2020 [citado 17/07/2024];96(1133):156-161. Disponible en: https://pubmed.ncbi.nlm.nih.gov/31801807/
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