Agonistas GLP-1 y protección oncológica en obesidad: revisión sistemática de mecanismos metabólicos, inflamación sistémica y evidencia clínica
Resumen
Introducción: La obesidad se asocia con incremento del riesgo de múltiples neoplasias mediante mecanismos metabólicos, inflamatorios, endocrinos e inmunológicos. Los agonistas del receptor del péptido similar al glucagón tipo 1 (GLP-1RA) han demostrado beneficios en reducción ponderal, control glucémico y mejoría cardiometabólica, lo que ha generado interés sobre su posible papel en la modificación del riesgo oncológico asociado a obesidad. Objetivo: Analizar la evidencia disponible sobre agonistas GLP-1 y protección oncológica en obesidad, con énfasis en mecanismos metabólicos, inflamación sistémica y evidencia clínica por tipo tumoral. Metodología: Se elaboró una revisión sistemática siguiendo principios PRISMA a partir de 30 referencias proporcionadas por los autores. Se incluyeron estudios observacionales, cohortes poblacionales, ensayos emulados, revisiones sistemáticas, metaanálisis, revisiones traslacionales y estudios preclínicos relacionados con GLP-1RA, obesidad y cáncer. Resultados: La evidencia poblacional sugiere asociaciones potencialmente favorables entre GLP-1RA y menor riesgo de algunos cánceres vinculados a obesidad, aunque los hallazgos no son uniformes por tipo tumoral. Los estudios sobre cáncer de mama, tiroides, esófago y neoplasias gastrointestinales muestran resultados heterogéneos y requieren interpretación específica. La evidencia mecanística respalda una posible protección indirecta mediada por pérdida de peso, reducción de resistencia a la insulina, control glucémico y atenuación de la inflamación sistémica. Los datos sobre tirzepatida y señalización GLP-1 en cáncer colorrectal son prometedores, pero aún exploratorios. Conclusión: Los GLP-1RA representan terapias metabólicas con posible impacto indirecto sobre factores asociados a carcinogénesis en obesidad. Sin embargo, la evidencia actual no permite considerarlos agentes oncopreventivos directos. Se requieren estudios prospectivos con seguimiento prolongado, desenlaces oncológicos preespecificados y análisis estratificados por tipo tumoral.
Descargas
Citas
Levy S, Attia A, Elshazli RM, Abdelmaksoud A, Tatum D, Aiash H, et al. Differential Effects of GLP-1 Receptor Agonists on Cancer Risk in Obesity: A Nationwide Analysis of 1.1 Million Patients. Cancers [Internet]. 2024 Dec 30;17(1):78. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11720624/
Wang L, Xu R, Kaelber DC, Berger NA. Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes. JAMA Network Open [Internet]. 2024 Jul 5;7(7):e2421305. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820833
Dai H, Li Y, Lee YA, Lu Y, George TJ, Donahoo WT, et al. GLP-1 Receptor Agonists and Cancer Risk in Adults With Obesity. JAMA Oncology [Internet]. 2025 Oct 1;11(10):1186. Available from: https://jamanetwork.com/journals/jamaoncology/article-abstract/2837870
Mads Gamborg, Grand MK, Grell K, Rosthøj S, Ulrik Pedersen-Bjergaard, Torp-Pedersen C, et al. Long-term cancer risk in users of GLP-1 agonists in Denmark: a nationwide emulated trial. The Lancet Regional Health - Europe [Internet]. 2025 Jun 14;55(Vol. 55):101346–6. Available from: https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762%2825%2900138-3/fulltext
Xande JG, del Giglio A. GLP-1 Receptor Agonists in Breast Cancer: A New Frontier in Obesity and Prognosis Management. International Journal of Molecular Sciences [Internet]. 2025 Aug 11;26(16):7744. Available from: https://www.mdpi.com/1422-0067/26/16/7744
Valencia-Rincón E, Rai R, Chandra V, Wellberg EA. GLP-1 receptor agonists and cancer: current clinical evidence and translational opportunities for preclinical research. Journal of Clinical Investigation [Internet]. 2025 Nov 3;135(21). Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12578377/
Hardvik Åkerström J, Santoni G, von Euler-Chelpin M, Birgisson H, Ness-Jensen E, Kauppila JH, et al. Glucagon-Like Peptide-1 Receptor Agonist Treatment and Risk of Esophageal Cancer. American Journal of Gastroenterology [Internet]. 2025 Dec 12; Available from: https://pubmed.ncbi.nlm.nih.gov/41384845/
Pasternak B, Wintzell V, Hviid A, Eliasson B, Gudbjörnsdottir S, Jonasson C, et al. Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study. BMJ [Internet]. 2024 Apr 10;385:e078225. Available from: https://pubmed.ncbi.nlm.nih.gov/38683947/
Kristensen SL, Rørth R, Jhund PS, Docherty KF, Sattar N, Preiss D, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. The Lancet Diabetes & Endocrinology [Internet]. 2019 Oct;7(10):776–85. Available from: https://pubmed.ncbi.nlm.nih.gov/31422062/
Wilbon SS, Kolonin MG. GLP1 Receptor Agonists—Effects beyond Obesity and Diabetes. Cells [Internet]. 2023 Dec 28;13(1):65. Available from: https://pubmed.ncbi.nlm.nih.gov/38201269/
Bezin J, Gouverneur A, Pénichon M, Mathieu C, Garrel R, Hillaire-Buys D, et al. GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care [Internet]. 2022 Nov 10;46(2):384–90. Available from: https://pubmed.ncbi.nlm.nih.gov/36356111/
Piccoli GF, Mesquita LA, Stein C, Aziz M, Zoldan M, Degobi NAH, et al. Do GLP-1 Receptor Agonists Increase the Risk of Breast Cancer? A Systematic Review and Meta-analysis. The Journal of Clinical Endocrinology & Metabolism [Internet]. 2020 Nov 28;106(3):912–21. Available from: https://pubmed.ncbi.nlm.nih.gov/33248445/
Parsons K, Montalvo M, Fischbach N, Taylor M, Alfaro S, Lustberg M. The Impact and Safety of GLP‐1 Agents and Breast Cancer. Cancer Medicine [Internet]. 2025 Jun;14(12). Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12186097/
Kamrul-Hasan ABM, Alam MS, Dutta D, Sasikanth T, Aalpona FTZ, Nagendra L. Tirzepatide and Cancer Risk in Individuals with and without Diabetes: A Systematic Review and Meta-Analysis. Endocrinology and Metabolism [Internet]. 2025 Feb 28 ;40(1):112–24. Available from: https://pubmed.ncbi.nlm.nih.gov/39814031/
Zhang Y, Xie Y, Xia S, Ge X, Li J, Liu F, et al. The Novel Dual GIP and GLP‐1 Receptor Agonist Tirzepatide Attenuates Colon Cancer Development by Regulating Glucose Metabolism. Advanced Science [Internet]. 2025 Mar 24;12(19). Available from: https://pubmed.ncbi.nlm.nih.gov/40125821/
Thomsen RW, Mailhac A, Løhde JB, Pottegård A. Real‐world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP ‐ 1RA ‐based weight‐loss therapies. Diabetes, Obesity and Metabolism [Internet]. 2025 Apr;27(S2):66–88. Available from: https://pubmed.ncbi.nlm.nih.gov/40196933/
Silverii GA, Marinelli C, Bettarini C, Del Vescovo GG, Monami M, Mannucci E. GLP ‐1 receptor agonists and the risk for cancer: A meta‐analysis of randomized controlled trials. Diabetes, Obesity and Metabolism [Internet]. 2025 May 29;27(8):4454–68. Available from: https://pubmed.ncbi.nlm.nih.gov/40437949/
Wali AF, Rangraze I, Khan S, Mufti UB, El-Tanani M, Rizzo M. Reassessing cancer risk with GLP-1 receptor agonists: a comprehensive meta-analysis of gastrointestinal malignancies. Frontiers in Pharmacology [Internet]. 2026 Feb 10;17. Available from: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1736380/full
Zhu C, Lai Y, Liu C, Teng L, Zhu Y, Lin X, et al. Comprehensively prognostic and immunological analyses of GLP-1 signaling-related genes in pan-cancer and validation in colorectal cancer. Frontiers in Pharmacology [Internet]. 2024 Jul 22;15. Available from: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1387243/full
Hernando-Requejo O, García de Quinto H. Obesity and its relationship with cancer. Nutrición Hospitalaria [Internet]. 2024; Available from: https://pubmed.ncbi.nlm.nih.gov/39279764/
Monami M, Dicembrini I, Nreu B, Mannucci E. Glucagon-like peptide-1 receptor agonists and malignancies: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2017;19(1):123–30. Available from: https://pubmed.ncbi.nlm.nih.gov/27699825/
Koehler JA, Baggio LL, Cao X, Abdulla T, Campbell JE, Secher T, et al. Glucagon-like peptide-1 receptor agonists increase pancreatic mass by induction of protein synthesis. Diabetes. 2015;64(3):1046-56. Available from: https://pubmed.ncbi.nlm.nih.gov/25277394/
Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740-56. Available from: https://pubmed.ncbi.nlm.nih.gov/29617641/
Nreu B, Dicembrini I, Tinti F, Mannucci E, Monami M. Pancreatitis and pancreatic cancer in patients treated with glucagon-like peptide-1 receptor agonists: an updated meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2020;165:108235. Available from: https://pubmed.ncbi.nlm.nih.gov/32720500/
Ligumsky H, Amir S, Arbel Rubinstein T, Guion K, Scherf T, Karasik A, et al. Glucagon-like peptide-1 analogs activate AMP kinase leading to reversal of the Warburg metabolic switch in breast cancer cells. Med Oncol. 2024;41(6):138. Available from: https://pubmed.ncbi.nlm.nih.gov/38705935/
Sharma, N., Khatib, M. N., Balaraman, A. K., Roopashree, R., Kaur, M., Srivastava, M., Barwal, A., Prasad, G. V. S., Rajput, P., Syed, R., Sharma, G., Kumar, S., Singh, M. P., Bushi, G., Chilakam, N., Pandey, S., Brar, M., Mehta, R., Sah, S., Gaidhane, A. M., … Shabil, M. (2025). Effect of GLP-1 receptor agonists on prostate cancer risk reduction: a systematic review and meta-analysis. International urology and nephrology, 57(4), 1039–1049. https://doi.org/10.1007/s11255-024-04266-4
Piccoli, G. F., Mesquita, L. A., Stein, C., Aziz, M., Zoldan, M., Degobi, N. A. H., Spiazzi, B. F., Lopes Junior, G. L., Colpani, V., & Gerchman, F. (2021). Do GLP-1 Receptor Agonists Increase the Risk of Breast Cancer? A Systematic Review and Meta-analysis. The Journal of clinical endocrinology and metabolism, 106(3), 912–921. https://doi.org/10.1210/clinem/dgaa891
Wang, L., Xu, R., Kaelber, D. C., & Berger, N. A. (2024). Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes. JAMA network open, 7(7), e2421305. https://doi.org/10.1001/jamanetworkopen.2024.21305
Levy, S., Attia, A., Elshazli, R. M., Abdelmaksoud, A., Tatum, D., Aiash, H., & Toraih, E. A. (2024). Differential Effects of GLP-1 Receptor Agonists on Cancer Risk in Obesity: A Nationwide Analysis of 1.1 Million Patients. Cancers, 17(1), 78. https://doi.org/10.3390/cancers17010078
Thomsen, R. W., Mailhac, A., Løhde, J. B., & Pottegård, A. (2025). Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies. Diabetes, obesity & metabolism, 27 Suppl 2(Suppl 2), 66–88. https://doi.org/10.1111/dom.16364
Derechos de autor 2026 Ixchel Lorena Guevara Galindo , María Fernanda Álvarez , Gibran Reynoso Hernández , Sergio Javier Alzugaray Gonzales , Frida Desiree Lara Hernández , María del Carmen Gómez García , Guadalupe Alejandra Villagómez Ramírez, Mayra Isabel Moreno Bautista, Ricardo Pulido Guerrero
Esta obra está bajo licencia internacional Creative Commons Reconocimiento 4.0.
.png)
.png)
1.png)
