AOD9604 Explained: Main Benefits, Dosages & Use Cases

*The below article and information are based on lab research data of AOD9604, this is not medical advice in any kind of shape or form.

AOD9604 is short for “Anti-Obesity Drug 9604”. You’d think the name says it all. But it doesn’t. 

The question that sparked the research that eventually led to the creation of AOD9604 was simple enough. What if we could take the massive growth hormone molecule and isolate only the bit home to its fat-burning signals? 

The path there was a lot harder, but a team at Metabolic Pharmaceuticals did it. AOD9604 is the last  15 amino acids in the GH chain — all the parts that get fat burning going and block new fat from being built, and none of the parts that increase insulin sensitivity. 

AOD9604 wasn’t the pure fat burner scientists had wanted to make, though. As studies — a large phase II human trial among them — progressed, it became clear that AOD9604 also had a surprising tissue repair talent. The discovery that AOD9604 sped up cartilage healing (usually slow as molasses) forever took it out of the “single-purpose peptide” box. 

Other obesity management peptides have since joined the list of options. Some of them are a whole lot more effective at inducing dramatic weight loss than AOD9604 — but that in no way earns this peptide a spot on the discard pile. If peptides had a tag line, we know exactly what it would be. “Expect the unexpected.” AOD9604 started off as a fat burner (and it’s still used to study lipolysis; more about that later), but it’s become even more interesting in the fields of pain management and regenerative medicine. 

An Interesting & Short History of AOD9604

Professor Frank Ng and his team at Monash University were ambitious — and a little ahead of their time. They wanted to make a targeted peptide with the potential to become the holy grail of weight loss. 

It didn’t happen by accident. They started off by deconstructing a 191-amino acid colossus. Human growth hormone itself. We’re sure not every part of that research was quite as exciting as it sounds, but they made a breakthrough when they found out that the amino acids 176-191 were the ones with all the metabolic promise. They’d found the “on switch” for fat burning. 

With half the battle won, they had to extend its half life. Tyrosine substitution was the tweak that stabilized the fragment — and the tweak that gave it research potential. They christened their peptide Anti-Obesity Drug 9604, filled with hope that the new compound would do exactly what it was made for. 

A slew of early studies — which culminated in a Phase IIb trial — focused on its weight loss effects. The results were positive, and studies also established that most subjects tolerated AOD9606 very well. It was safe, but the weight loss effect wasn’t quite strong enough to turn AOD9604 into the “miracle drug” the team that developed it was after. [1]

So, the end of the story?

Absolutely not. 

Those researchers who had really been paying attention noticed something strange in their models. Evidence of cartilage repair. AOD9604 induces lipolysis (it zaps fat, only in a more targeted way than other fat loss peptides), but it’s also a healer. Research didn’t stop. It expanded.

So, How Does AOD9604 Actually Work?

We’ll take a look at some of the most interesting findings so far in a little while — but those results are more interesting when you know what AOD9604 does. 

First, this stabilized GH fragment communicates with fat cells in pretty much the same way as the natural growth hormone floating around bodies everywhere. It does that very precisely, so that it can send the message to zap fat and stop making more. AOD9604 sends these signals without spiking blood sugar levels or changing insulin resistance, and that’s the part that makes it safer than GH itself. 

Then (this is the part that researchers didn’t see coming), AOD9604 also boosts chondrocyte production and nudges these cartilage building cells to make more collagen — while sending out anti-inflammatory signals. That’s why it’s gained a reputation as a healer. 

AOD9604 isolates two benefits of a serious growth hormone boost — and it manages to do that without touching the complications its massive parent molecule can bring along for the ride. “Nifty” doesn’t begin to cut it, and it’s no surprise that researchers from multiple fields have lined up to study it. 

Current Real-life Research Applications for AOD9604 (and What Could Be Next)?

We’ve already well and truly spoiled the plot twist. AOD9604 was developed as a weight loss compound, but it soon became a healer, too. Research into the full potential of this exciting peptide started in the ‘90s, and it’s never stopped since. 

AOD9604 for Obesity and Targeted Fat Zapping 

The research direction that opened the door to all others. Studies — and you’ll find a lot of them — confirmed that AOD9604 fights fat on two fronts. First, it stimulates lipolysis. It orders fat cells to make themselves available for energy, so they disappear. Then, it blocks the opposite process. AOD9604 works on the beta-3 adrenergic receptor and receptor sites on fat cells to stop the creation of new fat. Human trials reached the Phase IIb stage. [2, 3] Participants in five centers across Australia were able to lose significant amounts of weight — and AOD9604 has an excellent safety profile. [4]

The reason you don’t hear a lot more about it? The results weren’t quite as dramatic as with newer GLP-1 peptides (like Semaglutide, Tirzepatide, etc.), science moved onto those, instead. That doesn’t mean metabolic researchers have no use for the compound. It’s super clean (AOD9604 resculpts fat stores without messing with insulin or glucose), and it’s still of interest to investigators in fields where targeted fat loss is more important than maximum weight loss (not everyone who benefits from lipolysis needs to lose 10 to 20 percent of starting body weight). The fact that AOD9604 blocks lipogenesis also makes it a possible candidate for weight maintenance research. There’s more, though, and research into that “more” is picking up steam right now.

Osteoarthritis and Cartilage Repair Research: The Unexpected

It’s still early days for this particular research area, but osteoarthritis models have proven that AOD9604 has two very interesting effects on joint health. It makes chondrocytes, the cells that build cartilage, proliferate. It also gets more type II collagen made — the type of collagen that gives structure to cartilage. [5, 6]

That’s exciting, because it means that AOD9604 creates a “healing environment” — one where damaged surfaces can repair themselves more easily. The hope is that AOD9604 might slow the course of osteoarthritis (a progressive disease) down and reduce associated pain. This peptide might even turn out to be a disease-modifying osteoarthritis drug, that is, the type of compound rheumatology researchers have been dreaming of because it helps tackle root causes instead of only reducing symptoms. [7] Watch this space, because you may very well see AOD9604 developed as a peptide injected directly into joints to slow damage and speed up healing. 

But AOD9604 Has Potential Cardiovascular Benefits, Too

This is true for most compounds with proven weight loss effects, and the bulk of the effect is indirect. Treat overweight or obesity successfully, and lipid profiles improve. But AOD9604 might boost heart health more directly. Two things should catch your attention. AOD9604 promotes fat burning, but it’s also demonstrated inflammation-fighting effects. Even more interesting here is the blocking action that AOD9604 has demonstrated — it limits energy absorption. [8]

What’s Next?

Based on the known effects of AOD9604 and the areas of medicine sorely in need of new treatments? We suspect AOD9604 will continue to be researched in the area of weight management. Multi-peptide research protocols that combine AOD9604 with a GLP-1 agonist could lead to results neither peptide enables on its own. 

In the areas of sports medicine and rheumatology, the cartilage healing benefits of AOD9604 might be paired with an all-round healer like BPC-157 or TB-500 to observe if similar combined effects exist. Beyond that? The anti-aging potential is already drawing real interest, too. Muscle loss and fat gain with age are common. But perhaps not inevitable. Research into AOD9604 as a compound that can improve metabolic health and slow age-related muscle loss is only logical. 

How Have AOD9604 Studies Administered the Peptide?

To make sure that AOD9604 can reach the tissues targeted in research — fat deposits and joints, for instance — it’s important to make sure the peptide can freely circulate. The delivery method that makes this possible is subcutaneous or IM administration. 

Studies use subQ injection, and researchers haven’t tried to develop oral tablets or nasal sprays, because that’s what makes it bioavailable. Oral AOD9604 would get broken down by stomach acids immediately. Intranasal delivery is viable for compounds that mostly need to work in the brain, but not for systemic ones like AOD9604. 

How Do Researchers Determine Dosing Protocols for AOD9604?

The dosing that best allows researchers to study how the compound reacts in relation to their objectives depends on what those objectives are. The Phase II research that studied AOD9604 as an obesity treatment used doses of 1 mg, once a day — for 12 weeks or longer. That dose was determined safe and most effective, exactly the kind of balance researchers were looking for. 

Study designs that investigate how AOD9604 influences joint health (osteoarthritis and beyond) can use very similar dosing, because that 1 mg appears to be sufficient to trigger healing mechanisms as well. Where animal models are used, the human dose is translated according to the subject’s body weight. It’s possible that future studies will experiment with higher AOD9604doses to see if those improve the regenerative effects further, too. 

Longevity and biohacker enthusiasts researched doses:

• Those that didn’t have major healing or obesity reduction need – most start with ~0.3mg per day for 1-3 months.
• Some anecdotal experiences that needed more of peptide’s effects experimented with ~0.5-1mg per day for the same 1-3 months period.

AOD9604 — The Fat Burning Peptide That Turned Out to Do More

Systemic effects + clean safety profile = endless research potential. That’s the most exciting thing about AOD9604 . Human trials have proven that AOD9604 does what it was made for. It burns fat and keeps that fat off by blocking lipogenesis — and although it’s not as potent as newer GLP-1 peptides, the targeted action has clear applications. 

The current focus, however, lies somewhere else. In the field of regenerative orthopedics. From one holy grail (weight loss) to another (disease-modifying osteoarthritis treatment), AOD9604 has already made plenty of waves. The researchers who see its potential have one job — to keep the discoveries coming. 

FAQs

Scientific References and Sources

1. https://www.researchgate.net/profile/Jason-Halford/publication/7154334_Obesity_drugs_in_clinical_development/links/09e4150694f5675e10000000/Obesity-drugs-in-clinical-development.pdf[↩]
2. https://www.tandfonline.com/doi/abs/10.1517/14728214.10.3.643[↩]
3. https://www.sciencedirect.com/science/article/abs/pii/S1740677304000415[↩]
4. https://www.researchgate.net/profile/Antigone-Kouris-Blazos/publication/51376578_Health_economics_of_weight_management_Evidence_and_cost/links/59f6e243458515547c2327d9/Health-economics-of-weight-management-Evidence-and-cost.pdf[↩]
5. https://imtj.gmu.ac.ir/browse.php?a_id=3621&sid=1&slc_lang=en&html=1[↩]
6. https://utoronto.scholaris.ca/items/1ab5818e-ccf6-4a4b-a7cf-c4e0a75f186e[↩]
7. https://www.sciencedirect.com/science/article/abs/pii/S1043661808001047[↩]
8. https://onlinelibrary.wiley.com/doi/abs/10.1111/obr.12163[↩]