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Regulatory and compounding status All three compounds IGF-1 LR3, DES(1-3) IGF-1, and PEG-MGF share the same regulatory status in the United States: none have FDA-approved pharmaceutical formulations

5 The one exception in these stacks is GHK-Cu, which can be used indefinitely when applied topically

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Excretion Pathways Excretion mechanisms for both peptides remain incompletely characterized: Renal filtration likely represents primary elimination route for peptide fragments Hepatic metabolism may contribute to peptide degradation and clearance No evidence of significant biliary excretion in available studies Pharmacokinetic studies in renal or hepatic impairment models are absent from literature The rapid systemic clearance of both peptides contrasts with prolonged downstream effects on growth hormone and IGF-1, indicating that direct peptide presence is not required for sustained biological activity once pituitary signaling cascades are initiated

*Correspondence: Zhigang Li, [email protected] These authors have contributed equally to this work ORCID ID: Zhigang Li, orcid.org/0009-0001-0254-8155 Disclaimer All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers

BPC 157 enhances growth-hormone receptor expression in tendon fibroblasts