70% of American adults are considered overweight by the U.S. Centers for Disease Control and Prevention.
These people have belly fat and chub rub that they want to get rid of.
However, they struggle with their fluctuating weight, especially as they age, as this comes with increased stress and slower metabolism.
If you’re someone who likewise wants to lose 10 pounds and get rid of that unwanted fat, chances are that you’ve tried weight loss regimens in the past that failed you.
Fortunately, researchers from Australia and Denmark have discovered two of the best weight loss solutions that you can use, along with implementing a healthy diet and exercise, to help you successfully shed those pounds and inches.
We’re talking about AOD-9604 and ipamorelin, two of the safest and most effective peptides to help you get back in your best shape without putting your health at risk.
In this article, we’re diving into AOD 9604 vs Ipamorelin to help you figure out which one comes out on top for your weight loss goals.
What is Ipamorelin?
Ipamorelin is a pentapeptide that is considered a growth hormone-releasing peptide (GHRP) or growth hormone secretagogue (GHS).
This peptide, developed by Novo Nordisk and Helsinn Therapeutics, mimics the body’s natural release of ghrelin and growth hormone by targeting the ghrelin receptor in the pituitary gland.
Among all peptides in the GHS class, ipamorelin is considered one of the safest peptide therapies because it has no effect on the release and synthesis of other hormones in the body, such as aldosterone, acetylcholine, prolactin, and cortisol.
Apart from its weight loss benefits, ipamorelin is also widely used to enhance sports performance, manage certain illnesses, and fight the effects of aging.
It is even one of the most-used peptides, as it has a longer half-life than many, providing a more potent effect.
When you get injected with ipamorelin, a pulse is sent to the pituitary gland, signaling your body to release growth hormone.
When this happens, cells move toward the muscles to support development while minimizing your risk of having any cartilage or bone deformities.
Moreover, this peptide boosts ghrelin and insulin levels as well as cell synthesis, promoting muscle growth, strength, and fat loss.
As of this moment, ipamorelin is not approved by the FDA for commercial use.
What is AOD-9604?
AOD-9604, also known as Anti-Obesity Drug-9604, is a synthetic analog of the human growth hormone developed by Metabolic Pharmaceuticals.
It’s mainly used to fight obesity and help people who want to lose weight.
As an anti-obesity drug, it stimulates the pituitary gland to speed up the body’s metabolism for faster weight loss.
Apart from that, AOD-9604 also stimulates lipolysis, the body’s natural fat-burning process, to break down (triglycerides) fats stored in adipose tissue into fatty acids and glycerol.
As a result, it helps you burn fat while boosting your energy.
AOD-9604 is not approved by the FDA for commercial use, although qualified experts can buy and use it for research purposes.
Ipamorelin vs AOD-9604 Peptides Compared
Both peptides ipamorelin and AOD-9604 can help with weight loss but both have different mechanisms and effects.
Weight Loss
Ipamorelin boosts hGH levels within 40 minutes by stimulating GHS-R1a in the pituitary gland.
The peptide has a 2-hour half-life, and the effects of hGH last up to 3 hours.
Ipamorelin can boost serum GH, body weight, and appetite.
As shown in one study, taking ipamorelin can increase your appetite, resulting in muscle and fat gain.
In fact, it causes a 54% increase in 1GF-1 and reduced loss of muscle strength in drug-induced catabolic conditions.
Growth hormone secretagogues (GHSs) stimulate growth hormone (GH) secretion, which is lipolytic. Here we compared the effects of twice daily s.c. treatment of GH and the GHS, ipamorelin, on body fat in GH-deficient (lit/lit) and in GH-intact (+/lit and +/+) mice.
In +/lit and lit/lit mice ipamorelin induced a small (15%) increase in body weight by 2 weeks, that was not further augmented by 9 weeks. GH treatment markedly enhanced body weight in both groups. Ipamorelin also increased fat pad weights relative to body weight in both lit/lit and +/lit mice.
Two weeks GHS treatment (ipamorelin or GHRP-6) also increased relative body fat, quantified by in vivo dual energy X-ray absorpiometry (DEXA) in GH-intact mice. GH decreased relative fat mass in lit/lit mice and had no effect in GH-intact mice.
Treatment with GHS, but not GH, increased serum leptin and food intake in GH-intact mice. Thus, GHSs increase body fat by GH-independent mechanisms that may include increased feeding.
On the other hand, AOD-9604 works by increasing lipolysis in the body without any effect on hGH or IGH-1 synthesis.
This mechanism is similar to the results of doing exogenous hGH therapy, which also increases lipolysis in adipocytes and activation and adrenergic receptors.
AOD-9604 helps with weight loss due to fat loss.
This has been shown in test animals, where obese Zucker rats lost around 50% of weight in just 19 days. They had a 23% increase in lipolytic activity.
A synthetic analogue (AOD9604) of the lipolytic domain of human growth hormone (hGH) has been studied for its metabolic actions in obese Zucker rats.
Daily treatment with an oral dose of AOD9604 of 500 microg/kg body weight for 19 days reduced over 50% (15.8 +/- 0.6 vs. 35.6 +/- 0.8 g) body weight gain of the animals in comparison with the control.
The adipose tissues of the AOD9604–treated animals were found to have an increase in lipolytic activity. In contrast to chronic treatment with intact hGH, chronic treatment with AOD9604 showed no adverse effect on the insulin sensitivity of the animals, as demonstrated with euglycemic clamp techniques.
The results in the present study suggest that the analog of the hGH lipolytic domain may have the potential to be developed into an orally usable and safe therapeutic agent for obesity.
This means that ipamorelin can induce weight and muscle gain, while AOD-964 is useful for weight loss.
Benefits
Aside from helping with weight loss, ipamorelin and AOD-9604 also have other benefits.
AOD-9604 can provide therapeutic benefits to people with osteoarthritis and other bone disorders. It promotes collagen production and cartilage regeneration, which are important in bone strength, joint health, and bone repair.
The peptide helps slow down cartilage degeneration. Since it can help promote bone and cartilage repair, the peptide is believed to reverse some damage caused by degeneration.
In fact, in a study published in the Annals of Clinical & Laboratory Science, rabbits with osteoarthritis who were given AOD-9604 and hyaluronic injection for 8 weeks showed faster regeneration of cartilage.
The four groups showed different gross morphological damage and histopathological changes in the cartilage of the lateral part of the femoral condyle.
Complete disorganization of articular cartilage with apparent cloning of chondrocytes in the transitional and radial zones was evident in Group 1.
Abnormal gross morphological and histopathological changes such as fibrillated and irregular cartilage surfaces, disappearance of surface-layer cells, and slightly diffused cell growth in the transitional and radial zones were observed in Group 2.
Erosion of the articular cartilage, cleft, and cell cloning in the transitional and radial zones were noted in Group 3.
Softening of articular cartilage and surface irregularities were noted in Group 4.
Mature New Zealand white rabbits (n=32) were randomly administered 2 mg collagenase type II twice in each knee joint.
Weekly injections of 0.6 mL saline (Group 1), 6 mg HA (Group 2), 0.25 mg AOD-9604 (Group 3), and 0.25 mg AOD-9604 with 6 mg HA (Group 4) were administered for 4-7 weeks after the first intra-articular collagenase injection.
The degree of cartilage degeneration was assessed using morphological and histopathological findings, and the degree of lameness was observed at 8 weeks after the first collagenase injection.
Mean gross morphological and histopathological scores in Group 1 were significantly higher than those in Groups 2, 3, and 4 (p<0.05).
Mean gross morphological and histopathological scores in Group 4 were significantly lower than those in Groups 2 and 3 (p<0.05).
We found that osteoarthritic rabbits administered intra-articular AOD-9604 injections had better outcomes with lesser morphological and histopathological damage than was observed in the control group.
AOD-9604 is a disulphide-constrained peptide that comprises 15 amino acids from the C-terminal sequence of human GH and an additional N-terminal tyrosine residue: YLRIVQCRSVEGSCGF.
On the other hand, ipamorelin has more benefits than just helping you lose weight.
If you want to improve your body composition, ipamorelin can help you lose fat while gaining a higher percentage of lean muscle mass. This is the reason why athletes and bodybuilders opt for ipamorelin injections.
According to a study published in the European Journal of Endocrinology, ipamorelin can increase GH levels, promoting muscle growth and development.
Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) that displays high GH-releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry program, ipamorelin was identified within a series of compounds lacking the central dipeptide Ala-Trp of growth hormone-releasing peptide (GHRP)-1.
In vitro, ipamorelin released GH from primary rat pituitary cells with a potency and efficacy similar to GHRP-6 (ECs) = 1.3+/-0.4nmol/l and Emax = 85+/-5% vs 2.2+/-0.3nmol/l and 100%).
A pharmacological profiling using GHRP and growth hormone-releasing hormone (GHRH) antagonists clearly demonstrated that ipamorelin, like GHRP-6, stimulates GH release via a GHRP-like receptor. In pentobarbital anesthetized rats, ipamorelin released GH with a potency and efficacy comparable to GHRP-6 (ED50 = 80+/-42nmol/kg and Emax = 1545+/-250ng GH/ml vs 115+/-36nmol/kg and 1167+/-120ng GH/ml).
In conscious swine, ipamorelin released GH with an ED50 = 2.3+/-0.03 nmol/kg and an Emax = 65+/-0.2 ng GH/ml plasma.
Again, this was very similar to GHRP-6 (ED50 = 3.9+/-1.4 nmol/kg and Emax = 74+/-7ng GH/ml plasma). GHRP-2 displayed higher potency but lower efficacy (ED50 = 0.6 nmol/kg and Emax = 56+/-6 ng GH/ml plasma). The specificity for GH release was studied in swine.
None of the GH secretagogues tested affected FSH, LH, PRL, or TSH plasma levels. Administration of both GHRP-6 and GHRP-2 resulted in increased plasma levels of ACTH and cortisol.
Very surprisingly, ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation.
This lack of effect on ACTH and cortisol plasma levels was evident even at doses more than 200-fold higher than the ED50 for GH release.
In conclusion, ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. The specificity of ipamorelin makes this compound a very interesting candidate for future clinical development.
Ipamorelin also supports a healthy skeletal frame and protects you from possible bone disorders.
This has been shown in a study in The Journal of Clinical Endocrinology and Metabolism, where children who were deficient in growth hormone had improved bone density after 8 months of ipamoreline administration.
Six prepubertal children with GHD and growth failure received stepwise increasing sc doses of GHRP-2, at 0.3, 1.0, and 3.0 μg/kg/day, in successive 2-month treatment periods, with monitoring of overnight 12 h episodic GH secretion and toxicity measures at the end of each period.
During a fourth 2-month period, they received 3 μg/kg GHRP-2 together with 3 μg/kg sc GHRH. Serum levels of IGF-I and IGFBP-3 were also measured, and stadiometer height measurements were recorded. GHRP-2 administration produced a dosewise increase in overnight GH secretion.
GH profiles showed that the effect of GHRP-2 injections was relatively brief, with little effect upon GH secretion later in the night.
Serum levels of IGF-I and of IGFBP-3 did not increase.
Growth velocity was higher during GHRP-2 treatment than during pre-treatment and post-treatment evaluations. There were no side effects or toxicities observed.
Thus, GHRP-2 is well tolerated and is able to stimulate GH secretion.
Formulations or routes of administration that allow for a longer duration of action will likely be needed to use GHRP-2 in therapy.
Similarly, a study showed that rats given ipamorelin had induced longitudinal bone growth, as published in Growth Hormone & IGF Research.
To investigate the effects on longitudinal bone growth rate (LGR), body weight (BW), and GH release, ipamorelin in different doses (0, 18, 90, and 450 μg/day) was injected s.c. three times daily for 15 days to adult female rats.
After intravital tetracycline labeling on days 0, 6, and 13, LGR was determined by measuring the distance between the respective fluorescent bands in the proximal tibia metaphysis.
Ipamorelin dose-dependently increased LGR from 42 μm/day in the vehicle group to 44, 50, and 52 μm/day in the treatment groups (P<0.0001). There was also a pronounced and dose-dependent effect on BW gain.
The treatment did not affect total IGF-I levels, IGFBPs, or serum markers of bone formation and resorption.
The number of tartrate-resistant acid phosphatase-positive multinuclear cells in the metaphysis of the tibia did not change significantly with treatment.
The responsiveness of the pituitary to a provocative i.v. dose of ipamorelin or GHRH showed that the plasma GH response was marginally reduced (P<0.03) after ipamorelin but unchanged after GHRH.
Moreover, ipamorelin also supports digestive health and gastrointestinal function.
In a study published in the World Journal of Gastroenterology, the peptide ipamorelin was shown to help protect digestive health from various types of ulcers.
This was shown in male Wistar rats, preventing mucosal bleeding erosion after taking ipamorelin.
Male Wistar rats for 6 h induced serious gastric mucosal lesion [lesion area, WRS 81.8 ± 6.4 mm2 vs normal control 0.0 ± 0.0 mm2, P < 0.01], decreased the heart rate, and increased the heart rate variability and gastric acid secretion, suggesting an increase in vagal nerve-carrying stimuli.
GHRP-6 pre-injection via IP 2 h before the start of WRS dramatically prevented the WRS-induced mucosal bleeding erosion; only very slight or no hemorrhaging was observed in the WRS + GHRP-6 group.
The HE stains of the gastric tissues also confirmed that the mucosal injury/hemorrhage was minimal or not observed in WRS rats pre-treated with GHRP-6. Planimetry analyses showed that the lesion area was large in the WRS group but minimal in the WRS + GHRP-6 group; lesion area was zero in the SR group.
GHRP-6 did not have a protective effect on the mucosa of WRS rats if administered centrally via ICV, suggesting that the protective effect of GHRP-6 is mainly peripheral.
GHRP-6 alleviated the changes of HRV parameters induced by WRS and decreased the gastric acid output during WRS, suggesting that GHRP-6 protects the mucosa, at least in part, by suppressing the vagal efferent effect on the stomach.
GHRP-6 could alleviate the intensity of gastric stress response, which is reflected by the level of expression of HSP70 in the mucosa.
Western blotting results showed that both the WRS and SR induced a high expression of HSP70 in the gastric mucosal tissues, indicating a nonspecific response of HSP70 expression to stress.
GHRP-6 pretreatment significantly decreased the protein level of HSP70 in the WRS rats, suggesting a decrease in stress intensity.
Ipamoreline also supports healthy blood sugar levels by boosting GH secretion.
In a study in The Journal of Clinical Endocrinology and Metabolism, diabetic patients who were given ipamorelin showed improvement in their blood sugar levels.
Six type 1 diabetic males and six age-, sex-, and body mass index-matched control volunteers were studied.
Each subject received GHRH (100 μg iv), GHRP-6 (90 μg iv), and GHRH plus GHRP-6 on three separate days. GH peak values were higher in DM 1 patients than in control volunteers after GHRH (52.2 ± 9.8 vs. 19.3 ± 6.0μ g/L; P = 0.016), GHRP-6 (66.2 ± 9.6 vs. 39.9 ± 6.3 μg/L; P = 0.05) and GHRH plus GHRP-6 (81.8 ± 4.4 vs. 53.7 ± 8.2 μg/L; P = 0.01).
An additive GH response to combined administration of these two peptides was observed in diabetic patients.
Serum insulin-like growth factor (IGF)-1 levels were diminished in DM 1, with respect to normal subjects (145.2 ± 21.5 vs. 269.7 ± 42.0 μg/L; P = 0.01), whereas IGF-binding protein-3 levels were not significantly different between DM-1 and controls.
In summary, GHRP-6 is a potent stimulus for GH secretion in DM 1. The combined administration of GHRP-6 plus GHRH constitutes the most powerful stimulus for GH secretion in DM 1.
These patients exhibit a greater GH secretory capacity than normal subjects, probably caused by a diminished tone in the IGF-1 sustained negative feedback control exerted upon somatotroph responsiveness.
Lastly, the peptide ipamoreline has regenerative properties that can help repair damaged tissue caused by physical trauma or sporting injuries.
In fact, it can help boost collagen production, speeding up the wound-healing process.
Transforming growth factor-/spl beta/1 (TGF-/spl beta/1) is believed to be a key player in wound healing, promoting cell proliferation, migration, and matrix synthesis in a variety of cell types.
We have designed two peptides, i.e., cytomodulin-1 (CM-1) and cytomodulin-2 (CM-2), to simulate the binding domain of TGF-/spl beta/1.
In this study, we examined the bioactivity of the two synthetic peptides CM-1 and CM-2 on human foreskin fibroblasts (HFF).
Synthetic peptides CM-1 and CM-2 in culture media increased wound healing of fibroblasts in an injury model in vitro.
In addition, CM-1 and CM-2 enhanced the gene expression of collagen I and increased the production of pro-collagen I peptide in HFF.
These results suggest that CM-1 and CM-2 have potentially useful clinical applications in wound healing.
In other words, if you want to lose weight and enjoy other therapeutic benefits, ipamorelin is your best choice.
Side Effects and Safety
Ipamorelin and AOD-9604 have recorded no adverse side effects, except those that are common for first-time users, including headache, drowsiness, nausea, and vomiting.
As long as you take ipamorelin and AOD-9604 properly at the right dosage and for the right amount of time, you will experience minimal to zero side effects.
AOD 9604 vs Ipamorelin: Overall Winner
If you’re aiming to drop pounds and get rid of your belly fat and chub rub, both AOD-9604 and ipamorelin can help you out, although they work in slightly different ways.
AOD-9604 primarily targets fat burning and lipolysis, while ipamorelin aids weight loss by promoting muscle growth.
Your choice between AOD 9604 vs ipamorelin should align with your specific goals. If your primary focus is weight loss, AOD-9604 might be the better option.
However, if you’re looking to build muscle while trimming down, ipamorelin could be the more suitable choice.
Make sure to pair your peptide with a proper diet and active lifestyle for the best results.
If you’re in search of the best AOD-9604 and ipamorelin peptide, we recommend Limitless Life Nootropics, as they have some of the best formulations of AOD-9604 and ipamorelin peptides on the market.
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