Peptide comparison
AOD-9604 vs Semaglutide
AOD-9604 and Semaglutide are both research peptides. This side-by-side compares their mechanism, typical research dosing, half-life, routes and safety so you can see how they differ. For research use only.
| AOD-9604 | Semaglutide | |
|---|---|---|
| Category | Metabolic | Metabolic |
| Overview | A synthetic C-terminal fragment of human growth hormone studied for fat metabolism; failed its pivotal obesity trial but has human safety data and FDA food-ingredient GRAS... | GLP-1 receptor agonist with strong human-trial evidence for weight loss, glycemic control, and cardiovascular risk reduction. |
| How it works | AOD-9604 was designed to retain the lipolytic (fat-mobilising) domain of hGH while shedding the portions responsible for growth and metabolic side effects. The compound has been confirmed to NOT bind the growth hormone receptor — it cannot displace hGH from its receptor in binding assays and does not dimerize the receptor — and does NOT elevate circulating IGF-1. It also does not affect blood glucose or insulin sensitivity, which distinguished it from full-length hGH. AOD-9604 stimulates lipolysis and inhibits lipogenesis in adipose tissue. In preclinical studies, it inhibits acetyl-CoA carboxylase, the rate-limiting enzyme in de novo fatty acid synthesis, and activates hormone-sensitive lipase, promoting triglyceride breakdown. In obese mice, it upregulates beta-3 adrenergic receptor (beta-3 AR) mRNA expression in adipose tissue; however, Heffernan et al. (2001) demonstrated using beta-3 AR knockout mice that acute lipolytic effects persist in the absence of beta-3 AR, indicating that beta-3 AR upregulation is a downstream consequence rather than the primary signalling mechanism. The upstream receptor or intracellular signalling cascade directly activated by AOD-9604 has not been fully characterised in published literature. These mechanisms are established in vitro and in animal models. The failure of the pivotal human trial to demonstrate statistically significant weight loss at the oral doses tested means that extrapolation of preclinical fat-loss findings to human outcomes cannot be made. | Semaglutide selectively activates the GLP-1 receptor, mimicking the incretin hormone GLP-1. It enhances glucose-dependent insulin secretion and suppresses glucagon release (lowering blood glucose with low intrinsic hypoglycemia risk), slows gastric emptying, and acts on appetite-regulating centers in the hindbrain and hypothalamus to increase satiety and reduce food intake. The glucose-dependent nature of its insulinotropic effect means insulin is stimulated mainly when blood glucose is elevated. Its long duration of action is driven by albumin binding and resistance to enzymatic degradation rather than by a different receptor target. |
| Half-life | Intravenous half-life is approximately 3 minutes in pig models — consistent with rapid peptidase degradation. No peer-reviewed human pharmacokinetic study with specific half-life values for subcutaneous dosing has been published. A stable serum metabolite (the fragment CRSVEGSCG) is more persistent than the parent compound and is the target for anti-doping detection (Cox et al., 2015). A widely cited community figure of ~30 minutes for SC half-life appears unsourced from any peer-reviewed human PK study. | ~1 week (~160 hours) |
| Dosing reference | No approved clinical dosing exists. In Phase 1 single-dose studies, IV/SC doses of 25–400 mcg/kg were evaluated. Phase 2a oral studies tested 1, 5, 10, 20, and 30 mg/day. The pivotal Phase 2b OPTIONS trial used 0.25 mg, 0.5 mg, and 1.0 mg orally daily — none of which demonstrated statistically significant weight loss vs placebo. The GRAS designation covers oral use as a food ingredient at up to 1 mg/person/day. No dose has been established as therapeutically effective. | For type 2 diabetes (Ozempic), subcutaneous dosing typically starts at 0.25 mg once weekly for 4 weeks (a non-therapeutic initiation dose), increasing to 0.5 mg/week, then up to 1 mg or 2 mg/week as needed and tolerated. For chronic weight management (Wegovy), a stepwise 16-week escalation is used: 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, then a 2.4 mg/week maintenance dose. Slow titration is emphasized to limit gastrointestinal side effects; rapid escalation has been linked to severe GI complications including gastroparesis. |
| Routes | subcutaneous, oral | subcutaneous, oral |
| Safety & side effects | AOD-9604 has one of the more characterised short-term human safety profiles among research peptides, by virtue of having been through six controlled clinical trials in ~893 subjects. Across all trials, no serious adverse events were attributed to the drug, no dose-dependent adverse effects were identified, and the rate of common mild adverse events (headache, GI symptoms) was statistically indistinguishable from placebo. No subjects developed anti-AOD-9604 antibodies. No effects on IGF-1, insulin, blood glucose, or bone density markers were observed. However, long-term safety beyond the trial durations (up to 24 weeks) has not been evaluated. Subcutaneous injection risks (infection, injection-site reactions) apply to any injectable research compound, and product quality of unregulated material is an inherent risk. AOD-9604 is NOT approved as a drug. The FDA has reviewed it and it does not appear on the list of bulk drug substances eligible for compounding (Category 1); compounding pharmacies have received warning letters for dispensing it. In Australia it is a TGA prescription-only substance. AOD-9604 is explicitly named on the WADA Prohibited List under S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics — specifically as a growth hormone fragment) and is prohibited at all times in competitive sport, with no therapeutic use exemption pathway available. Products are for research use only and not for human consumption. | Most common side effects are gastrointestinal: nausea, vomiting, diarrhea, constipation, and abdominal pain, usually mild-to-moderate and most pronounced during dose escalation. More serious but less common risks include acute pancreatitis, gallbladder disease (cholelithiasis/cholecystitis), and, with rapid dose escalation, gastroparesis. Hypoglycemia risk rises when combined with insulin or sulfonylureas. In rodents semaglutide caused dose-dependent thyroid C-cell tumors; human relevance is considered low, but it is contraindicated in those with personal/family history of medullary thyroid carcinoma or MEN 2, and in pregnancy. Worsening diabetic retinopathy was noted in SUSTAIN-6. Rapid weight loss may contribute to lean-mass loss. Use only under medical supervision; gray-market product carries purity and dosing-accuracy risks. |
For research use only. Not for human consumption. Always verify against current literature.