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The Arg3 to Leu3 substitution disrupts a key contact residue in the IGFBP binding interface, and the N-terminal extension further sterically interferes with binding pocket access

The microneedling component carries its own risks independent of PTD-DBM

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Moreover, this study also raises awareness of the risks of gastrointestinal adverse events induced by GLP-1RAs, and safety concern is especially warranted for high dose administration