AOD-9604, MOTS-c and retatrutide: trial outcomes
A side-by-side look at the questions that actually reached human studies.
Human study questions
A comparison by reputation would put all these molecules under metabolism and lose the useful distinctions. I’d rather line up the study questions. AOD-9604 reached a human obesity program that failed to show statistically significant weight loss. MOTS-c’s dialysis cohort measured a naturally circulating marker. Retatrutide’s Phase 2 program measured several treatment outcomes.
| Compound | Human evidence collected here | What it establishes |
|---|---|---|
| AOD-9604 | Human safety and tolerability program | Placebo-like tolerability; the pivotal obesity endpoint failed. |
| MOTS-c | Observational dialysis cohort | A biomarker association with a composite of all-cause mortality and non-fatal cardiovascular events; no peptide was administered. |
| Retatrutide | Obesity trial, diabetes trial and liver-fat substudy | Defined Phase 2 treatment outcomes in the populations studied. |
The columns describe different projects. They cannot support a head-to-head choice of treatment.
A completed negative result
AOD-9604 poses the least fashionable question: how much weight does a completed negative program carry after its mechanism becomes popular again? For me it carries a great deal. The mouse knockout result remains interesting biology, while the human obesity program supplies the answer for demonstrated weight-loss efficacy.
The oral human trials and the animal experiments also used different routes and contexts. Relabeling the molecule as a research peptide leaves that history intact.
A failed human endpoint is information. AOD-9604 gives this comparison more than an attractive mechanism.
A measured circulating marker
The MOTS-c cohort involved 94 chronic hemodialysis patients followed for a median of 26.5 months. Measuring a substance already in circulation answers an association question. Giving that substance and measuring outcomes would answer an intervention question.
I’m particularly wary of letting the word human do all the work in a description of this paper. The people, illness, measured marker and lack of administration specify its scope. The CK2 experiments add cell-free and mouse evidence about mechanism, without filling the human-intervention gap.
Distinct retatrutide endpoints
Retatrutide’s obesity trial reports mean body-weight change over 48 weeks. Its diabetes trial reports HbA1c at 24 weeks and weight at 36 weeks. Its MASLD substudy reports relative liver-fat change at 24 weeks. Different subjects and time points produce different answers, even when the molecule has the same name.
I’d resist flattening those papers into a single success score. Gastrointestinal effects, heart rate, body composition and long-term outcomes belong alongside the result they qualify. The retatrutide page takes those endpoints separately.
Approval and prescription context
All three compounds lack FDA approval in the regulatory record maintained here. AOD-9604’s obesity program was discontinued. MOTS-c’s compounded prescription route depends on individual assessment by a U.S.-licensed clinician; some requests are declined, care is U.S.-only, availability depends on state and treatment, and compounded medication has no FDA approval. Retatrutide remains an investigational drug in Phase 3 development in the mid-2026 status recorded here.
FDA’s page current as of April 22, 2026 records withdrawn compounding nominations for AOD-9604 and MOTS-c, retaining safety concerns. A withdrawn nomination establishes no permission to compound. None of this comparison provides medical advice or a personal dose.