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In particular, GLP-1R agonism not only emerged as a powerful tool in the treatment of T2D and excess adiposity but also displayed favorable effects on the cardiovascular system and neurodegenerative diseases. Research and development of GLP-1R agonists single receptor interventions Despite its substantial in vitro and in vivo benefits, native GLP-1s use in pharmacological interventions was hampered by its extremely limited half-life (~2-3 min), with studies estimating that even in sustained administration, only 10% of active GLP-1 enters general circulation, and even less reaches its target organ the brain