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and promotion of muscle mitochondria biogenesis.The potential for GLP-1R agonists to improve muscle function and architecture underscores the need for large randomized controlled, clinically comparative trials of GLP-1R agonists in patients with IIM.

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Conclusions Hypomorphic PAM T2D-risk alleles reduce amidating enzyme activity, elevate circulating GLP-1 levels, and impair GLP-1 post-receptor signaling, culminating in a selective and clinically meaningful reduction in GLP-1RA efficacy