Plaza Florido, AbelLindholm, Malene E.Carrera Bastos, PedroSantos Lozano, AlejandroValenzuela, Pedro L.Fiuza Luces, María del CarmenRadom Aizik, ShlomitLucía Mulas, Alejandro2026-07-182026-07-182026Plaza-Florido, A., Lindholm, M. E., Carrera-Bastos, P., Santos-Lozano, A., Valenzuela, P. L., Fiuza-Luces, C., Radom-Aizik, S., & Lucia, A. (2026). Exercise pills for cardiometabolic health cannot mimic the exercise milieu. Trends in Endocrinology & Metabolism, 37(4), 356-370. https://doi.org/10.1016/j.tem.2025.07.0051043-27601043-2760https://hdl.handle.net/11268/17288Physical exercise can play an important role both in primary and secondary cardiovascular disease prevention by virtue of its multisystem effects. These beneficial adaptations at the whole-body level include improvements in mitochondrial health, vascular function, and autonomic balance, together with attenuation of inflammation and the release of ‘exerkines’ with pleiotropic effects. Thus, several research groups have attempted to develop so-called ‘exercise pills’ or ‘exercise mimetics’: that is, substances that are theoretically capable of reproducing some of the cardiometabolic benefits associated with regular exercise. In this review we summarize pharmacological and phytochemical agents which, when used alone or in combination with exercise, may improve cardiometabolic health. We also discuss the current gaps and future steps needed to translate these findings into therapeutic applications.engAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/Ciencias del DeporteEjercicio FísicoEnfermedades CardiovascularesFactores de Riesgo Cardiometabólicojournal article10.1016/j.tem.2025.07.005open accessCiencias médicasFisiología humanaFarmacologíaGoal 3: Ensure healthy lives and promote well-being for all at all agesGoal 9: Build resilient infrastructure, promote sustainable industrialization and foster innovation