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Due to its dual-receptor mechanism, more real-world data is still needed to support its long-term safety

Furthermore, since the instability of Ala 2 is caused by degradation of DPP-4, Ala 2 may not need to be changed if the peptide is fused with albumin or Fc domain (discussed later) for long-term activity, which creates a steric hindrance to prevent the enzyme from getting close

ROS can exert multiple effects on the immune system, including the activation and interaction of immune cells, host defense, and immune suppression 150

On the other hand, GLP-1R signaling in astrocytes was proven to be essential for maintaining mitochondrial integrity and function of the hypothalamic astrocytes, as deletion of GLP-1Rs resulted in the adaptive cellular stress response with the improvement of glucose metabolism and memory formation [97]