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Consistent with the findings that intestinal AMPK, which mediates NAMPT activation, is impaired in glucose intolerance, HFD-induced obesity, and aging downregulates the major NAD + -generating enzymes, including NAMPT, and reduces intestinal NAD + levels [31,99,100]

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Future direction: Multi target combination and cell therapy To overcome current limitations, the "central plan" intervention for GLP-1RA is moving towards the following directions: Multi target agonist development GLP-1/GIP/GCGR triple target agonists (such as Retatrutide) have entered phase III clinical trials, and their weight loss effect is expected to reach 22% -24%

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