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mechanism unexplained Relative contributions of direct peptide effects versus downstream IGF-1 actions inadequately characterized Long-term receptor sensitivity and potential for desensitization inadequately studied Individual patient variability in response not well-characterized Potential for differential effects based on endogenous growth hormone status unclear Long-Term Safety Considerations Critical safety questions remain unanswered regarding chronic peptide administration: Cardiovascular safety concerns – FDA warnings cite risks of increased heart rate, systemic vasodilation, flushing, and transient hypotension Immunogenicity risks – FDA identifies both peptides as potentially immunogenic with risk of serious immune reactions including anaphylaxis Cancer risk – theoretical concern that chronic growth hormone/IGF-1 elevation could promote cellular proliferation