Evidence Grade C — Moderate human evidence. 239 published studies, 133 human. 4 registered clinical trials.
Medically reviewed by a licensed medical professional
MOTS-c is a peptide encoded in the mitochondrial genome, discovered in 2015 as part of a newly identified class of mitochondrial-derived peptides. Research in animal models suggests effects on metabolic regulation. No human clinical trials have been conducted. The field is young and the science is still at an early stage.
MOTS-c is also known by these brand and alternate names:
239 published studies: 133 human, 52 animal, 30 in-vitro, 50 reviews
MOTS-c has no marketing authorisation. No human clinical trials have been conducted. The evidence base consists entirely of animal studies and cell culture experiments, primarily from the laboratory that discovered the peptide in 2015.
Human observational studies have reported correlations between circulating MOTS-c levels and metabolic parameters, but observational correlations do not establish therapeutic potential. The compound is of scientific interest as part of the emerging field of mitochondrial-derived peptides, but clinical translation has not been attempted. Products available through unregulated channels lack pharmaceutical quality assurance.
Research in animal models and cell culture suggests MOTS-c may interact with metabolic signalling pathways including AMPK activation. It was identified as a mitochondria-encoded signalling molecule, representing a novel form of communication between mitochondria and the cell nucleus. These observations are entirely preclinical.
Research in animal models and cell cultures suggests MOTS-c may interact with metabolic signalling pathways, particularly AMPK activation. Human observational studies have found correlations between circulating MOTS-c levels and metabolic parameters, but correlations do not establish therapeutic potential. No human clinical trials have been conducted. Most research originates from the laboratory that discovered the peptide. Independent replication is needed. The field of mitochondrial-derived peptides is young (since 2015), and MOTS-c's biological role and therapeutic relevance remain to be determined. Products from unregulated channels lack pharmaceutical quality assurance.
PeptideTrace tracks 4 registered clinical trials for MOTS-c sourced from ClinicalTrials.gov.
MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity
The Cardiovascular Effect of GLP-1 Agonist, SGLT2 Inhibitor and Their Combination
Cohort Of DEafness-gene Screening
Platelet Reactivity, B-amyloid, MOTS-c and Mortality of Type II Diabetics With CAD
MOTS-c (Mitochondrial ORF of Twelve S rRNA type-c) is a 16-amino-acid mitochondrial-derived peptide encoded in 12S rRNA gene. MW ~2,174 Da. One of a growing class of bioactive peptides from mitochondrial genome short ORFs. Discovered by Cohen group at USC 2015. Circulating levels decline with age. Not approved.
Research suggests mitochondrial retrograde signaling: translocates to nucleus under metabolic stress, interacting with AMPK and NRF2 pathways. Activates AMPK, phosphorylating ACC to enhance fatty acid oxidation. Increases AICAR via folate-methionine cycle modulation. In skeletal muscle: insulin-independent glucose uptake, improved sensitivity, enhanced exercise capacity. Prevented age/HFD-induced insulin resistance in mice.
No marketing authorization. No human trials. Lee et al. (Cell Metabolism 2015): prevented DIO and insulin resistance in mice (5 mg/kg IP x7 days, -8% weight, improved glucose tolerance). Reynolds et al. (2021): restored exercise endurance in aged mice. Kim et al. (JASN 2019): renal protection. Human observational: lower levels in T2DM and with aging.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
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Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.
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Glucagon has been available as an emergency injection since the 1960s and remains the standard rescue treatment for severe hypoglycaemia. Recent innovation has focused on making it easier to administer in emergencies. Baqsimi, approved in 2019, was the first needle-free option as a nasal powder. Gvoke, also approved in 2019, eliminated the need to mix and reconstitute the medication before injection — a significant advance since severe hypoglycaemia often impairs the ability to follow complex preparation steps. Dasiglucagon (Zegalogue), a next-generation stable liquid glucagon approved in 2021, further improved on the convenience of rescue administration. Beyond emergency rescue, glucagon's receptor is now a major research target — dual and triple agonists combining glucagon receptor activity with GLP-1 (such as survodutide and retatrutide) are in advanced clinical trials for obesity and metabolic disease.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
