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Lack of Human Clinical Data The most significant limitation is the near-complete absence of published human clinical trial data: No peer-reviewed human efficacy trials exist in scientific literature as of 2025 One analog compound (CB4211) completed Phase 1 safety testing, but results not published in peer-reviewed journals Human optimal dosing, safety profile, and efficacy completely unestablished Long-term effects of exogenous MOTS-c administration in humans unknown No published data on human absorption, distribution, metabolism, or excretion While endogenous MOTS-c levels have been measured in human populations and exercise studies confirm its physiological presence, therapeutic use remains entirely experimental

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non-significant) in clinical decision-making and to provide more intuitive data for individualized counseling, we conducted an exploratory Bayesian NMA, intended as a PoC, which introduces the ROPE to translate heterogeneous clinical evidence into posterior probabilities of achieving or exceeding predefined clinical thresholds

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