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However, long-term use is associated with challenges such as motor fluctuations, dyskinesias, and loss of therapeutic efficacy due to progressive neurodegeneration and alterations in dopaminergic pathways

However, in keeping with our data on receptor pharmacology, increasing the dose to 30 nmol kg 1 , tenfold higher than maximal doses from our studies, shows that tirzepatide does have insulinotropic activity in Glp1r -/- mice or in the presence of a GLP-1R antagonist 5 , demonstrating that tirzepatide can engage the GIPR in mouse beta cells at sufficiently high concentrations

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doi: 10.1089/ars.2009.2510

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