Fat Loss & Metabolism

AOD-9604 is a synthetic peptide fragment consisting of amino acids 176-191 from the C-terminus of human growth hormone (hGH) with a tyrosine residue added at the N-terminus. Developed by Metabolic Pharmaceuticals Limited, it was designed to mimic hGH's lipolytic (fat-burning) properties without stimulating IGF-1 production or causing insulin resistance. The peptide operates by activating beta-3 adrenergic receptors in adipose tissue, promoting lipolysis while inhibiting lipogenesis. Initial 12-week clinical trials showed modest weight loss (average 2.6 kg vs 0.8 kg placebo), but a larger 24-week trial of 536 subjects failed to demonstrate significant efficacy, leading to termination of development in 2007. Despite lack of FDA approval, AOD-9604 remains available through compounding pharmacies and gray market sources. It is prohibited by WADA as a non-approved substance under category S.0. The peptide has shown potential applications beyond obesity, including cartilage repair in osteoarthritis models.

HGH Fragment 176-191 (AOD-9604) is a modified synthetic peptide fragment derived from the C-terminal region of human growth hormone (amino acids 176-191) that was developed to isolate the fat-reducing properties of HGH without its growth-promoting or insulin-antagonistic effects. This peptide stimulates lipolysis (fat breakdown) and inhibits lipogenesis (fat formation) by upregulating beta-3 adrenergic receptors in adipose tissue, which enhances fat oxidation and energy expenditure. While preclinical studies in rodents demonstrated significant reductions in body weight and fat mass, human clinical trials showed mixed results, with some short-term trials showing modest weight loss (2.6 kg over 12 weeks) but larger long-term trials failing to demonstrate statistically significant efficacy, leading to termination of its development as an approved obesity treatment in 2007. Despite not receiving regulatory approval for weight loss, the peptide has shown excellent safety and tolerability profiles across multiple clinical trials involving over 900 participants, with emerging research exploring potential applications in cartilage regeneration and osteoarthritis treatment.

Tirzepatide is a synthetic 39-amino acid polypeptide conjugated with a C20 fatty diacid moiety that functions as the first-in-class dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. Approved by the FDA in May 2022 for type 2 diabetes (brand name Mounjaro) and November 2023 for chronic weight management (brand name Zepbound), it demonstrates superior glycemic control and weight reduction compared to selective GLP-1 agonists. Clinical trials show dose-dependent weight loss of 15-21% and HbA1c reductions up to 2.58% over 40-72 weeks. The compound exhibits biased agonism, with greater affinity for GIP receptors and preferential cAMP signaling at GLP-1 receptors, contributing to enhanced beta-cell function and insulin sensitivity. In gray market contexts, tirzepatide is sold as a research chemical with significant quality and safety concerns, as unapproved versions lack FDA oversight for purity, sterility, and accurate dosing.

Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist with 94% structural homology to human GLP-1, featuring three key modifications that provide enzymatic stability and extended half-life of approximately one week. Approved by the FDA in multiple formulations (Ozempic for diabetes, Wegovy for obesity, Rybelsus as oral formulation), it functions by enhancing glucose-dependent insulin secretion, suppressing glucagon release, delaying gastric emptying, and reducing appetite through central and peripheral mechanisms. Semaglutide has demonstrated significant cardiovascular benefits with 20-26% risk reduction in major adverse cardiac events, substantial weight loss outcomes (14-17% body weight reduction), and improvements in glycemic control with HbA1c reductions of 1.0-1.8%. Despite its FDA-approved status, semaglutide has entered gray markets as a research chemical sold without prescription, with quality testing revealing dramatically substandard purity levels (7-14% versus claimed 99%), endotoxin contamination, and significant safety concerns regarding compounded and unregulated sources.

Tesamorelin is a synthetic analogue of human growth hormone-releasing hormone (GHRH) that stimulates the production and secretion of endogenous growth hormone from the pituitary gland. The peptide consists of all 44 amino acids of human GHRH with the addition of a trans-3-hexenoic acid group at the N-terminus, which enhances its stability in serum. It was approved by the FDA in November 2010 under the brand name Egrifta as the first and only treatment specifically indicated for reducing excess visceral abdominal fat in HIV-infected patients with lipodystrophy. Clinical trials have demonstrated significant reductions in visceral adipose tissue (15-37% relative reduction), along with improvements in triglycerides, liver fat, and metabolic markers. The peptide has also shown promising effects on cognitive function in older adults and individuals with mild cognitive impairment. Tesamorelin is administered as a once-daily subcutaneous injection and is commercially available by prescription for its FDA-approved indication, though it remains under investigation for additional therapeutic applications including non-alcoholic fatty liver disease and age-related cognitive decline.