Agonistas del receptor GLP-1 y neuroprotección: ¿prevenir o modificar las enfermedades neurodegenerativas?
DOI:
https://doi.org/10.66476/mf.v3n2.7537Palabras clave:
Receptor del Péptido 1 Similar al Glucagón, Enfermedades Neurodegenerativas, Demencia, Enfermedad de Parkinson, Atención Primaria de SaludResumen
Introducción: Los agonistas del receptor del péptido similar al glucagón tipo 1 (AR-GLP-1) muestran efectos neuroprotectores en modelos preclínicos y se asocian con menor demencia en estudios observacionales. Se desconoce si previenen o modifican las enfermedades neurodegenerativas.
Métodos: Revisión narrativa de la literatura desde 2020, con búsquedas en MEDLINE y Europe PMC (agosto y octubre de 2026), con cribado por título y resumen.
Resultados: Se identificaron 61 fuentes. Los datos de prevención provienen sobre todo de personas con diabetes tipo 2. Los estudios observacionales asociaron los AR-GLP-1 con menor riesgo de demencia, con HR de 0,30 sin comparador activo e intervalos que incluían el 1 con comparador activo. Entre los ensayos, no diseñados para evaluar cognición, un metaanálisis de 23 estudios halló menos demencia o deterioro cognitivo con AR-GLP-1 (OR 0,55); REWIND y GRADE no mostraron diferencias claras. En Parkinson, la mayoría de los estudios mostró menor riesgo (HR 0,68 a 0,81), pero dos cohortes no hallaron diferencia. En modificación, evoke y evoke+ no enlentecieron el Alzheimer; en Parkinson, dos ensayos de fase 2 fueron positivos, pero la fase 3 de exenatida y NLY01 fueron negativos, y la fase 3 tiene una expresión de preocupación sin resolver. Para la tirzepatida (agonista dual GIP/GLP-1) solo hay estudios observacionales.
Conclusiones: Los AR-GLP-1 tienen respaldo para sus indicaciones metabólicas. Para prevenir enfermedades neurodegenerativas la evidencia es insuficiente y no concluyente; para modificar el Alzheimer, negativa, y en Parkinson, discordante. En medicina familiar conviene prescribirlos por indicación y no prometer protección cerebral.
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Derechos de autor 2026 Ana Isabel Martínez Marmori, Yenny Lorena Esteche Dos Reis, Lida Romina Miranda, Patricia Lais Frighetto Nodari, Andrea Dionisia Franco Torres, Alba Melisa Silvero Pesoa, Diego Javier Álvarez Marecos, Rodney A. Lesme Portillo, Albert Rafael Barrail Hellman
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