AOD-9604

Typical use cases

Dosing guidelines

Titration

Community protocols commonly describe starting at a lower dose (e.g., ~250 mcg) and adjusting toward ~300-500 mcg/day based on tolerance, often run in cycles of several weeks. This is informational only, not a recommendation.

Reconstitution

Lyophilized powder reconstituted with bacteriostatic water (commonly ~2 mL per 5 mg vial); add water slowly down the vial wall and swirl gently rather than shaking to avoid foaming

Injection sites

Subcutaneous injection, typically into abdominal subcutaneous fat (rotating sites); some community use is localized to target fat areas

Storage & handling

Store lyophilized vials refrigerated (2-8 C) and protected from light; once reconstituted keep refrigerated and use within roughly 2-4 weeks. Do not freeze.

Side effects

• Injection-site reactions (redness, irritation) Mild · Common
• Headache Mild · Uncommon
• Gastrointestinal symptoms (diarrhea, flatulence, nausea) Mild · Uncommon
• Fatigue Mild · Uncommon
• Dizziness Mild · Rare
• Hypersensitivity / allergic reaction Moderate · Rare

Research summary

AOD-9604 (Tyr-hGH 177-191) corresponds to the C-terminal "lipolytic domain" of human growth hormone and was developed by Metabolic Pharmaceuticals as a candidate anti-obesity drug. Preclinical work in obese mice and Zucker rats reported that AOD-9604 (~500 µg/kg) reduced body-weight gain and increased adipose lipolysis without the insulin-desensitizing effects of intact hGH, and the effect appeared IGF-1-independent (Ng et al., Horm Res 2000; Heffernan et al., Endocrinology 2001). Six randomized, double-blind, placebo-controlled human trials enrolling roughly 900 subjects between 2001 and 2006 reported a safety/tolerability profile indistinguishable from placebo, no rise in IGF-1, no adverse effect on glucose tolerance, and no anti-drug antibodies (Stier et al., 2013). A 12-week Phase 2 oral study reported modest weight loss favoring low-dose (1 mg) AOD-9604 over placebo (~2.6 vs 0.8 kg), but the response was not dose-dependent, and a larger 24-week Phase 2b trial failed to separate from placebo on its primary endpoint; clinical development as a prescription obesity drug was discontinued around 2007 (Valentino et al., 2010). Pharmacokinetic data describe rapid degradation with a very short plasma half-life on the order of minutes. Important limitations: the strongest human data used oral formulations rather than the subcutaneous injections common in community settings, efficacy signals were small and inconsistent, and subsequent reviews concluded the compound did not produce clinically significant fat loss versus placebo. The compound was later promoted for limited food-ingredient/nutraceutical use under a self-affirmed GRAS approach (which is not FDA drug approval), and in 2024 an FDA advisory committee declined to add AOD-9604 to the 503A compounding bulk-substances list.

Key references

• https://academic.oup.com/endo/article-abstract/142/12/5182/2988749
• https://karger.com/hrp/article/53/6/274/371690/Metabolic-Studies-of-a-Synthetic-Lipolytic-Domain
• https://www.jofem.org/index.php/jofem/article/view/157/194
• https://jofem.org/index.php/jofem/article/view/213/278
• https://pmc.ncbi.nlm.nih.gov/articles/PMC3136748/
• https://pubchem.ncbi.nlm.nih.gov/compound/71300630

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