Independent · non-commercial · publishes on a quarterly cycle|Current cycle 2026 Q3
Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Compound monograph · §3

MOTS-c — clinical evidence

Assessed outcomes with certainty ratings, contributing trials and the reasoning for each rating.

Document identifier
CEI-MN-043/3
Series
Compound monograph
Version
1.0
Published
20 May 2024
Last reviewed
20 Aug 2025
Next review
20 Aug 2027
Identifier
10.71829/cei.mono.43
Certainty
Very low
Cycle
2024 Q2

§3Clinical evidence

Assessed outcomes for MOTS-cPoint estimates with confidence intervals for each contributing study, plotted against the line of no effect.0.00.20.40.60.8Standardised direction and relative magnitude of the recorded effectIndicationEffect as recordedAgeing0 trials · Very lowNo randomised controlled human trial…Obesity0 trials · Very lowNo randomised controlled human trial…Mitochondrial disease0 trials · Very lowNo randomised controlled human trial…Type 2 diabetes0 trials · Very lowNo randomised controlled human trial…
Moderate or high certaintyLow or very low certainty
Figure 3. Illustrative. Assessed outcomes plotted on a common standardised axis so that direction and relative magnitude can be compared at a glance. The estimates are not on a common natural scale and the intervals are the Institute's standardised representation of the reported precision, not the published confidence intervals. Published intervals appear in the per-indication extracts and in the text below.

§3.1Biological ageing and healthspan endpoints

Anchor outcome. Epigenetic age acceleration.

Effect as recorded. No randomised controlled human trial identified; —.[1,2]

Certainty. Very low certainty Observational associations between endogenous MOTS-c concentration and metabolic phenotype exist; these are associations, not intervention evidence.

Contributing trials. None identified. The rating reflects an absence of controlled evidence rather than conflicting evidence.

Full evidence extract for biological ageing and healthspan endpoints · Indication assessment

§3.2Obesity and overweight in adults

Anchor outcome. Percentage change in body weight from baseline.

Effect as recorded. No randomised controlled human trial identified; —.[2,3]

Certainty. Very low certainty Rodent diet-induced obesity models only.

Contributing trials. None identified. The rating reflects an absence of controlled evidence rather than conflicting evidence.

Full evidence extract for obesity and overweight in adults · Indication assessment

§3.3Primary mitochondrial myopathy and bioenergetic disorders

Anchor outcome. Six-minute walk distance.

Effect as recorded. No randomised controlled human trial identified; —.[3,4]

Certainty. Very low certainty

Contributing trials. None identified. The rating reflects an absence of controlled evidence rather than conflicting evidence.

Full evidence extract for primary mitochondrial myopathy and bioenergetic disorders · Indication assessment

§3.4Type 2 diabetes mellitus

Anchor outcome. Change in HbA1c (%, mmol/mol).

Effect as recorded. No randomised controlled human trial identified; —.[4]

Certainty. Very low certainty Rodent insulin-sensitivity findings only.

Contributing trials. None identified. The rating reflects an absence of controlled evidence rather than conflicting evidence.

Full evidence extract for type 2 diabetes mellitus · Indication assessment

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

  1. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism 2015;21(3):443–454. doi:10.1016/j.cmet.2015.02.009 · PMID 25738459
  2. D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089
  3. Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544–575. doi:10.1007/s11095-009-0045-6 · PMID 20143256
  4. Bhattacharyya S, Wang J, Kaplan RM. Quality of peptide products obtained from unregulated online suppliers: an analytical survey. Journal of Pharmaceutical Sciences 2024;113(4):1102–1110. doi:10.1016/j.xphs.2023.11.021 Cited by the Institute as an indicative analytical survey; sample frame was not random.

Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.

Nothing published by the Institute is medical advice, a diagnosis, a prescription, a treatment recommendation or a purchasing recommendation. Compounds supplied for research use are not approved for human or veterinary use in any jurisdiction, and a favourable analytical assessment of a supplier is not a statement that any product is safe or effective. The Institute publishes certainty ratings and never recommendations. No telephone number, messaging handle or ordering channel appears anywhere on this site.