MOTS-c vs AOD-9604: evidence, FDA review and sport rules

Not yet medically reviewed. Fact-checked against the sources listed below on October 7, 2026.How we write and review

Last updated October 7, 2026

MOTS-c is a mitochondrial peptide studied mainly in mice and cells, with one human trial still recruiting. AOD-9604 is a growth hormone fragment that reached phase 2b trials, but in its largest trial weight loss was not significantly different from placebo. Neither is in an FDA-approved drug, WADA bans both, and no FDA Philippines record was found for either.

Key takeaways

MOTS-c is a 16 amino acid peptide encoded by mitochondrial DNA and thought to act through the energy-sensing enzyme AMPK. AOD-9604 is a 16 amino acid fragment of human growth hormone proposed to increase fat breakdown.
AOD-9604 was tested in people in company-funded trials, up to phase 2b. In its largest trial (536 enrolled, 24 weeks), the US FDA reports no significant difference in weight loss from placebo.
The US FDA found no clinical studies giving MOTS-c to people. CB4211, a MOTS-c analog, completed a small trial whose results were reported only in company SEC filings, and a phase 2a trial of MOTS-c is recruiting in China.
The US FDA found too little human safety information for both and proposed keeping both off its list of substances allowed in pharmacy compounding.
WADA prohibits both at all times: AOD-9604 in class S2.2.3 (growth hormone fragments) and MOTS-c in class S4.4.1 (AMPK activators).
No record of either was found in FDA Philippines Verification Portal searches on October 7, 2026, and no FDA Philippines advisory naming either was found.

Side by side

	MOTS-c	AOD-9604
Class	Mitochondrial-derived peptide (16 amino acids) found naturally in the body; the synthetic version is investigational and not approved as a medicine	Synthetic 16 amino acid fragment of human growth hormone (the C-terminal region, with an added tyrosine); investigational, not approved as a medicine anywhere
FDA Philippines registration	No record found in an FDA Philippines Verification Portal search on October 7, 2026	No record found in an FDA Philippines Verification Portal search on October 7, 2026
Evidence	Animal and lab studies only	Phase 2 human trials
Prescription needed	Not confirmed	Not confirmed
Registration source date	Checked October 7, 2026	Checked October 7, 2026

How they work

Both are peptides of 16 amino acids, but they are unrelated molecules with different proposed actions.

	MOTS-c	AOD-9604
Origin	Encoded by a short stretch of the mitochondrial 12S rRNA gene. The body makes it naturally; the version the US FDA reviewed is synthetic	A synthetic fragment of human growth hormone (amino acids 177 to 191) with an added tyrosine
First described	2015, University of Southern California and UCLA researchers	Developed by Metabolic Pharmaceuticals. Animal studies published in 2000 and 2001
Proposed action	Inhibits the folate cycle and purine building in cells, which switches on AMPK, an energy-sensing enzyme. Main target organ appeared to be skeletal muscle	Increases fat breakdown and fat oxidation without binding the growth hormone receptor
Where the mechanism comes from	Cell and mouse studies	Mouse and rat studies, and company-funded human trials that found no effect on IGF-1
Known target	The US FDA says the molecular target "remains unknown"	Not acting through the growth hormone receptor or, by the authors' account, directly through the beta-3 receptor
Other names	Mitochondrial open reading frame of the 12S rRNA-c, MOTs-C	AOD9604, Tyr-hGH 177-191, hGH 176-191

For more detail, see the what are peptides guide.

Evidence compared

AOD-9604 was tested in people and did not show a significant effect on weight in its largest trial. MOTS-c has not yet completed a human trial. Neither has evidence of benefit in people in the sources checked.

	MOTS-c	AOD-9604
Highest stage reached	Phase 2a trial registered March 2026, recruiting	Phase 2b. The developer announced the results in February 2007
Human trials completed	None of MOTS-c itself. The US FDA found no clinical studies giving it to people	Six randomized, placebo-controlled trials with about 900 adults summarised in 2013, all funded by the developer
Main human result	None yet	Largest trial (536 enrolled, 24 weeks): the US FDA reports no significant difference in weight loss from placebo
Related analog	CB4211, tested by CohBar in 88 people (phase 1a/1b). Results reported only in SEC filings, not peer reviewed	None
Animal evidence	In male mice on a high-fat diet, 8 weeks of MOTS-c led to about 20% lower body weight than mice given an inactive control (vehicle) (US FDA summary). Other rodent studies on insulin resistance, bone and blood vessel calcification	Obese rats: weight gain fell by over 50% versus control over 19 days. Obese mice: less weight gain over 14 days. One rabbit knee osteoarthritis study
Published in journals	Animal and cell studies, yes. No human treatment results	Efficacy results of the phase 2b trials never published in a peer-reviewed journal
Development status	CohBar's 2022 annual report says it was exploring "strategic alternatives". No later CB4211 trial found	Developer ended development for obesity in February 2007

Who ran the research. Authors of the 2018 and 2021 MOTS-c papers declared consulting for and shareholding in CohBar, the company behind CB4211. The 2013 AOD-9604 safety summary was written by authors who worked for or consulted for its developer.

The US FDA's verdict on each. For AOD-9604 it concluded there is "a lack of evidence to support the effectiveness" for obesity. For MOTS-c it said the clinical relevance of the animal findings "is currently unknown".

Risks compared

For both, the US FDA says it lacks enough safety information to know whether they would cause harm in humans.

	MOTS-c	AOD-9604
US FDA overall view	"Potential safety risks associated with the use of MOTS-c in humans are unknown"	FDA "lacks sufficient information to know whether the drug would cause harm when administered to humans"
Animal toxicology	No repeat-dose toxicity, genotoxicity, reproductive or cancer-risk studies found	Possible bone effects in rats (13 weeks), possible liver toxicity signals in monkeys (9 months), equivocal mutagenic signals
Immune reactions	FDA concern when injected under the skin, from clumping and impurities. Antibodies could neutralize the body's own MOTS-c	FDA says it "may pose significant risk for immunogenicity for certain routes of administration"
Human side effects reported	No trial data. USADA cites anecdotal reports of increased heart rate or palpitations, injection site irritation, insomnia, immune reactions and fever	Headache, fatigue, dizziness, diarrhoea, flatulence, nausea and increased appetite in early studies. Five people on AOD9604 in one trial had cancers or growths reported, judged unrelated by the investigator (2013 summary by authors linked to the developer)
Analog trial	Phase 1a participants had "mild, but persistent injection site reactions" (company report)	Not applicable
FAERS reports	None found through March 9, 2025	None found through January 7, 2024
Product quality	Peptide aggregation and impurities flagged by the FDA	"Not physically and chemically well characterized". The nomination's certificate of analysis lacked impurity and endotoxin tests

A 2026 Sports Medicine review includes both among unapproved peptides marketed direct to patients and says "rigorous human safety data are scarce, and there is potential for serious harm to patients."

US FDA review compared

Both were nominated for use in US pharmacy compounding, both nominations were withdrawn, and the FDA reviewed both and proposed keeping them off its 503A bulks list. Its advisory committee voted against AOD-9604, but AJMC and DLA Piper reported that it voted to recommend adding MOTS-c. DLA Piper notes that committee votes are "non-binding recommendations" and that "FDA is not obligated to follow the AdComm's recommendations." No final FDA decision was found for either.

	MOTS-c	AOD-9604
Nominated for	Insulin resistance, obesity, osteoporosis, vascular calcification, muscle and fat metabolism, and longevity	Weight loss, osteoporosis and osteoarthritis
FDA safety risks page (April 22, 2026)	Listed under "Bulk drug substances nominated but withdrawn"	Listed under "Bulk drug substances nominated but withdrawn"
FDA's proposal	Physicochemical characterization, historical use and "lack of any safety and effectiveness information in humans" weigh against adding it to the 503A bulks list (2026)	Neither form should be added; use in compounding "may raise safety concerns" (2024)
Advisory committee	Reported by AJMC and DLA Piper (both July 31, 2026) to have voted on July 23, 2026 to recommend adding it. The reports give different counts, and the FDA had posted no minutes as of October 7, 2026	Voted 0 yes, 12 no, 0 abstain on December 4, 2024
Final FDA decision	None found	None found
US outsourcing facilities	Reported no MOTS-c products, January 2017 to December 2025	Reported no AOD-9604 products, 2017 to 2023
Marketing found by the FDA	Clinics marketing injectable MOTS-c for weight loss, glucose regulation, physical performance and slowing cellular aging	Wellness clinics and medical spas marketing it for osteoarthritis, osteoporosis, weight loss and anti-aging

Australia. The Australian Poisons Standard (June 2026) lists AOD-9604 in Schedule 4, prescription only medicines. No Australian entry for MOTS-c is recorded in the sources behind this page.

WADA classes compared

Both are prohibited at all times, in and out of competition, but in different classes.

	MOTS-c	AOD-9604
Class	S4.4.1, activators of AMP-activated protein kinase (AMPK), under S4.4 Metabolic Modulators	S2.2.3, growth hormone, its analogues and fragments
Wording on the 2026 list	"Activators of the AMP-activated protein kinase (AMPK), e.g. ... AICAR, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)"	"growth hormone fragments, e.g. AOD-9604 and hGH 176-191"
First named	2025 list (not named on the 2024 list)	Placed in S0 in a 2013 WADA statement. Named in S2 on the 2022 list, the earliest list checked
2027 list	Still named in S4.4.1	Same S2.2.3 entry
USADA	A Therapeutic Use Exemption is "highly unlikely" because there is no approved therapeutic use	Listed among peptides "not approved for human use by regulatory authorities" that are prohibited in sport
Testing	Plasma test validated by a Cologne anti-doping lab (2019)	Urine test validated (2015)

Athletes should check any substance with their national anti-doping organisation.

PH status compared

The FDA Philippines status of both is unverified.

	MOTS-c	AOD-9604
Verification Portal	No record found for "MOTS-c" on October 7, 2026. A search for "MOTS" found only an unrelated food product	No record found for "AOD9604" or "AOD-9604" on October 7, 2026
FDA Philippines website	Searches for "MOTS-c", "MOTS", "mitochondrial", "humanin" and "CB4211" returned no results	Searches for "AOD-9604", "AOD9604", "AOD 9604" and "growth hormone fragment" returned no results
FDA Philippines advisories	None found	None found
Prescription status	No Philippine source found	No Philippine source found

A search with no record is not an official FDA Philippines statement, and a missing advisory does not mean a product is registered or approved. To check any product, search the FDA Philippines verification portal at verification.fda.gov.ph. For more on Philippine rules, see are peptides legal in the Philippines.

What cannot be compared

The two tables above set the facts side by side, but some comparisons are not possible from the sources.

No shared trial. No study has tested MOTS-c and AOD-9604 together or against each other.
Different questions studied. AOD-9604's phase 2b trials looked at weight loss with the peptide taken by mouth. MOTS-c's only human treatment trial, still recruiting, looks at insulin sensitivity with injections.
Analog versus the real molecule. The only completed human treatment trial in the MOTS-c line used CB4211, a different molecule.
Different review dates. The FDA reviewed AOD-9604 in 2024 and MOTS-c in 2026.

Whether any treatment suits you is a decision for a licensed doctor.

Frequently asked questions

What is the difference between MOTS-c and AOD-9604?

MOTS-c is a peptide the body makes from mitochondrial DNA, and is thought to act through the energy-sensing enzyme AMPK. AOD-9604 is a lab-made fragment of human growth hormone that was designed to increase fat breakdown. Both have 16 amino acids, but they are unrelated molecules.

Have MOTS-c and AOD-9604 been tested in humans?

A 2013 summary covers six company-funded AOD-9604 trials with about 900 adults, up to phase 2b. The largest showed no significant weight difference from placebo, according to the US FDA. For MOTS-c, the US FDA found no clinical studies giving it to people.

Has MOTS-c or AOD-9604 been shown to cause weight loss in people?

Not in the sources checked. AOD-9604's largest trial found no significant difference from placebo, and its development for obesity stopped in 2007. MOTS-c reduced diet-induced obesity in mice, but no human trial results of MOTS-c itself exist yet.

Are MOTS-c and AOD-9604 approved by the US FDA?

No. The US FDA says neither is a component of an FDA-approved drug. Its advisory committee voted 0 to 12 against adding AOD-9604 to the 503A bulks list in December 2024. On July 23, 2026 it was reported by AJMC and DLA Piper to have voted to recommend adding MOTS-c. That vote is non-binding, and no final FDA decision was found as of October 7, 2026.

Are MOTS-c and AOD-9604 banned in sport?

Yes, both are prohibited at all times. WADA names AOD-9604 in class S2.2.3 as a growth hormone fragment and MOTS-c in class S4.4.1 as an activator of AMPK. MOTS-c has been named since the 2025 list.

Are MOTS-c and AOD-9604 legal in the Philippines?

Their status is unverified. No record of either was found in FDA Philippines Verification Portal searches on October 7, 2026, and no Philippine source on a prescription route was found. A search with no record is not an official FDA Philippines statement.

What are the risks of MOTS-c and AOD-9604?

The US FDA says it lacks the safety information to know whether either would cause harm in humans. It raised concerns about immune reactions and impurities for both. For AOD-9604 it also noted bone and liver signals in animal studies.

Is CB4211 the same as MOTS-c?

No. CohBar describes CB4211 as an analog of MOTS-c, a modified molecule. Its phase 1a/1b results come only from the company's SEC filings and were not peer reviewed, so they do not show what MOTS-c itself does.

Are there clinical trials of MOTS-c or AOD-9604 now?

A phase 2a trial of MOTS-c in adults with prediabetes and overweight or obesity was recruiting in China, with completion estimated for May 2028. A ClinicalTrials.gov search on October 7, 2026 found no AOD-9604 studies.

Sources

This content is for education only and is not medical advice. Talk to a licensed doctor before starting any treatment.