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For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement.
AMIRAVOResearch Library

AOD-9604 vs semaglutide

AOD-9604 and semaglutide are both peptides that have been studied in obesity research, but they come from unrelated pharmacology: AOD-9604 is a fragment of human growth hormone, while semaglutide is a GLP-1 receptor agonist 4,8. Semaglutide is an FDA-approved medicine with large randomized outcome trials, whereas AOD-9604 has no FDA approval and its development for obesity was terminated after a phase 2b trial did not separate from placebo 5,7,13. This page sets out how the two differ in structure, mechanism, evidence and regulatory status as of 22 October 2026.

Unbranded reference vial illustrating AOD-9604; not an actual product
AOD-9604
Not approved — research use only
Unbranded reference vial illustrating Semaglutide; not an actual product
Semaglutide
FDA-approved

Side by side

FieldAOD-9604Semaglutide
ClassGrowth hormone C-terminal fragment analog 4GLP-1 receptor agonist (GLP-1 analog) 8
Origin and structureSynthetic peptide of human GH residues 177-191 with an added N-terminal tyrosine 4GLP-1 analog with 94% sequence homology to human GLP-1; the backbone is made by yeast fermentation and carries a C18 fatty di-acid that promotes albumin binding 8
Proposed mechanismDescribed as a synthetic lipolytic domain of GH; in mice its lipolytic action was not mediated directly through the beta-3 adrenergic receptor 1,2Selectively binds and activates the GLP-1 receptor 8
Half-lifeNot identified in the sources reviewedApproximately 1 week 8,10
Highest human trial phasePhase 2b (OPTIONS, about 500 adults), with results described by FDA from a company announcement rather than a peer-reviewed paper 5Phase 3 randomized trials, including cardiovascular outcome trials 9,10,11
FDA statusNot approved; no Drugs@FDA application record returned on 22 October 2026; listed among compounding substances that may present significant safety risks (nomination withdrawn) 6,7Approved (Ozempic 2017, Rybelsus 2019, Wegovy 2021) 13
Published human outcomesFDA's 2024 review concluded that in most studies identified AOD-9604 did not show benefit over placebo for body-weight reduction 5In STEP 1 (1,961 adults without diabetes), mean body-weight change at week 68 was -14.9% versus -2.4% with placebo 9
Safety signalsFDA cites immunogenicity and impurity concerns, limited safety information, and serious adverse events of unclear causality 6Labels carry a boxed warning for thyroid C-cell tumors seen in rodents, of undetermined human relevance 8,12
WADA statusNamed in S2.2.3 as a growth hormone fragment; prohibited at all times 14Not named in the sections of the 2026 List reviewed (S0, S2, S4.4) 14
Evidence levelAnimal studies, plus small or abstract-only human studies summarized by FDA 1,2,5Multiple large randomized controlled trials in humans 9,10,11

AOD-9604: what the data says

AOD-9604 is a synthetic peptide made of the C-terminal residues 177-191 of human growth hormone with an added N-terminal tyrosine 4. In obese mice, 14 days of chronic administration reduced body weight and body fat, and the effect was absent in beta-3 adrenergic receptor knock-out mice during long-term treatment, which led the authors to conclude that its lipolytic action is not mediated directly through that receptor 1. In obese Zucker rats, 19 days of oral treatment reduced body-weight gain by over 50% compared with control, and, unlike intact GH, did not adversely affect insulin sensitivity on clamp testing (animal data) 2. A rabbit knee osteoarthritis model reported lower cartilage-degeneration scores with intra-articular AOD9604 (animal data) 3.

In humans, FDA's December 2024 advisory committee review summarized short developer-run studies and a 12-week trial in 300 adults reported only as an abstract, noting that methodological detail was insufficient 5. FDA also described a 24-week phase 2b study (OPTIONS, 536 enrolled) in which the change in body weight did not differ significantly from placebo, after which the developer terminated the obesity program in 2007 5.

Semaglutide: what the data says

Semaglutide is a GLP-1 analog that selectively binds and activates the GLP-1 receptor; its long action is attributed mainly to albumin binding, and a position-8 modification stabilizes it against dipeptidyl-peptidase 4 8. The labels state an elimination half-life of approximately 1 week 8.

In the STEP 1 phase 3 trial of 1,961 adults with overweight or obesity without diabetes, mean body-weight change at week 68 was -14.9% with semaglutide and -2.4% with placebo 9. In SUSTAIN-6 (3,297 adults with type 2 diabetes), the primary cardiovascular composite occurred in 6.6% versus 8.9% (hazard ratio 0.74) 10. In SELECT (17,604 adults with cardiovascular disease and overweight or obesity without diabetes), it occurred in 6.5% versus 8.0% (hazard ratio 0.80) 11. The labels describe a risk of thyroid C-cell tumors in rodents whose human relevance has not been determined 8,12.

Key research differences

  • Pharmacology: AOD-9604 is a growth hormone fragment studied for lipolytic effects, while semaglutide acts on the GLP-1 receptor 1,8.
  • Trial outcomes: semaglutide's phase 3 trials met their primary endpoints, whereas the AOD-9604 phase 2b trial described by FDA did not show a significant difference from placebo 5,9,11.
  • Publication: semaglutide trial results are published in peer-reviewed journals, while key AOD-9604 human results are known from abstracts and a company announcement summarized by FDA 5,9.
  • Regulatory status: semaglutide is FDA-approved, while AOD-9604 has no approval and is on FDA's list of compounding substances that may present significant safety risks 6,13.
  • Half-life: about 1 week for semaglutide; no figure was found for AOD-9604 8.
  • Sport: AOD-9604 is named as a prohibited GH fragment by WADA; semaglutide is not named in the sections reviewed 14.

Where the evidence is limited

No head-to-head study of AOD-9604 and semaglutide was identified, so any comparison is indirect. The AOD-9604 human evidence comes from short developer studies, an abstract-only trial and an unpublished phase 2b trial as summarized by FDA, and these lack the detail needed to evaluate them independently 5. Most mechanistic AOD-9604 data are from mice and rats 1,2. Semaglutide's evidence base consists of large, sponsor-funded randomized trials in specific populations, and its findings do not transfer to AOD-9604 9,10,11.

Frequently asked questions

Do AOD-9604 and semaglutide work the same way?
No. AOD-9604 is a fragment of human growth hormone described as a lipolytic domain, and semaglutide is a GLP-1 receptor agonist 2,8.
Has AOD-9604 been tested in humans?
FDA's 2024 review described short developer studies, an abstract-only 12-week trial and a 24-week phase 2b trial in which body-weight change did not differ significantly from placebo; development for obesity was terminated in 2007 5.
Is either one FDA-approved?
Semaglutide is approved as Ozempic, Rybelsus and Wegovy 13. No Drugs@FDA application record was returned for AOD-9604 on 22 October 2026 7.
Have they been compared directly?
No head-to-head trial was identified in the sources reviewed.
Are they prohibited in sport?
AOD-9604 is named as a growth hormone fragment in S2.2.3 of WADA's 2026 List; semaglutide is not named in the sections reviewed 14.

References

  1. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice Endocrinology. 2001
  2. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone Hormone Research. 2000
  3. Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model Annals of Clinical & Laboratory Science. 2015
  4. Detection and in vitro metabolism of AOD9604 Drug Testing and Analysis. 2015
  5. Pharmacy Compounding Advisory Committee Meeting, December 4, 2024: FDA presentations (including CJC-1295-related and AOD-9604-related bulk drug substances) FDA. 2024
  6. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026) FDA (Human Drug Compounding). 2026
  7. Drugs@FDA application data queried through openFDA for AOD-9604 (no matching application record returned) (queried 22 October 2026) openFDA / Drugs@FDA. 2026
  8. OZEMPIC (semaglutide) injection and tablets: prescribing information (Novo Nordisk) FDA label (DailyMed). 2026
  9. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) New England Journal of Medicine. 2021
  10. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6) New England Journal of Medicine. 2016
  11. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) New England Journal of Medicine. 2023
  12. WEGOVY (semaglutide) injection and tablets: prescribing information (Novo Nordisk) FDA label (DailyMed). 2026
  13. Drugs@FDA application records for NDA 209637 (Ozempic), NDA 213051 (Rybelsus) and NDA 215256 (Wegovy) Drugs@FDA (via openFDA). 2026
  14. International Standard: Prohibited List 2026 WADA. 2026

For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. This page compares published research and is not medical advice or a recommendation.