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Human Clinical Data Gaps No large-scale long-term safety studies in healthy adults No confirmed peer-reviewed primary studies from 2022 through 2024 appear in available sources Most trials conducted in specific subpopulations (elderly, GH-deficient, obese) with limited generalizability Short study durations relative to the chronic conditions being studied No cancer incidence data from long-term trials, despite documented IGF-1 elevation raising theoretical oncological concerns Mechanistic Uncertainties The brain’s counter-regulatory response (increased somatostatin) observed in rats has not been fully characterized in human subjects Whether this somatostatin response limits long-term GH-stimulating efficacy in humans is unknown Direct neuroprotective effects of MK-677 have not been confirmed in any reviewed human study Direct anti-inflammatory effects of MK-677 have not been confirmed in any reviewed human study Methodological Weaknesses The FDA has specifically noted that existing MK-677 studies feature small sample sizes, short durations, and lack of clinically meaningful therapeutic endpoints [7]