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However, this inhibitory effect is significantly weakened in patients with T2DM, indicating that its potential application in diabetes treatment requires further investigation
It has become a valuable tool in various stages of drug development, including first-in-human dose calculation, predicting DDI potential, and assessing pharmacokinetic profiles in special populations such as pediatrics and patients with renal or hepatic impairment.222,223 In particular, it is widely used to predict potential pharmacokinetic DDIs of small molecules.224 Physiological properties of the body, including organ mass and volume, blood flow rate, plasma protein levels, and the abundance of enzyme and transporter expression, are mathematically described within the model.225,226 Therefore, the mechanism of action of GLP-1 RAs and a dual GLP-1/GIP RA can be characterized by modulating physiological properties within the model, enabling the prediction of altered pharmacokinetics for the affected drug
Notably, -cell development is impaired in mice lacking Foxa2 but is normal in mice lacking Foxa1 [119,120]
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