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Exendin-4 significantly increased insulin level and phosphorylation of insulin receptor substrate 1 (IRS-1) in rat hippocampus, and could not change the status of tau phosphorylation without insulin in HT22 neurons, suggesting that insulin is required in reduction of tau hyperphosphorylation by GLP-1R agonists (154)

The limited duration and small sample size may have contributed to the lack of behavioral effects, and ongoing trials are exploring repeated dosing strategies (e.g., NCT06252623, NCT06691243)

The drug also tries to prevent other risks associated with elevated glucose

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30, when the FDA set a PDUFA date of May 9, 2024

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