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Reimbursement policies may contribute to the pattern of therapies observed at baseline, with restrictions based on BMI and previous/ongoing therapies such as metformin, sulphonylureas and/or basal insulin [37]

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

However, administering thyroid hormone systematically exposes to the risks of cardiotoxicity and bone loss mediated by THR- before any hepatic benefits can be seen

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10.1038/ijo.2013.162 181

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