HGH Fragment 176-191

The synthetic 16-residue C-terminal tail of human growth hormone, studied in rodents for antilipogenic and lipolytic activity and sold on the research market; its tyrosine-substituted analog AOD-9604 failed a Phase 2b obesity trial and neither form is approved anywhere.

Also referenced as: HGH Frag 176-191, GH fragment 176-191, Frag 176-191, hGH 176-191, hGH fragment 176-191

Also appears in: Metabolic

What is HGH Fragment 176-191?

HGH Fragment 176-191 is a synthetic 16-residue peptide copying the carboxyl-terminal tail of human growth hormone, from phenylalanine 176 through the final phenylalanine 191 of the 191-residue hormone (sequence FLRIVQCRSVEGSCGF). A disulfide bond between cysteine 182 and cysteine 189 closes a small ring, so the fragment is cyclic rather than linear. Biochemists at Monash University mapped this region of the hormone over more than two decades, first as the part of growth hormone that raises blood glucose and antagonizes insulin in rats, and later as a domain that inhibits fat synthesis and stimulates fat breakdown in adipose tissue without the growth-promoting activity of the intact molecule.

AOD-9604 is the development compound that Metabolic Pharmaceuticals built from this region: the 15-residue span hGH 177-191 with a tyrosine added at the amino terminus. Laid against the native 176-191 sequence, that is a single substitution, tyrosine in place of phenylalanine at the first position, with the same 15 residues and the same disulfide ring behind it. Most of the Monash animal work used either the 15-residue hGH 177-191 (later coded AOD9401) or the tyrosine analog AOD9604; the only metabolic study that tested the exact 176-191 sequence is the 1978 rat work on blood glucose. The research market sells peptides under the “fragment 176-191” name, citing the AOD-9604 literature after that program ended in 2007.

How it works

The fragment’s biology has been worked out almost entirely in rodent adipose tissue and in obese rodent models, mostly by one laboratory, and the mechanism differs from that of the full hormone in one important way: it does not act through the growth hormone receptor.

• Antilipogenic activity concentrated in the C-terminal domain — synthetic hGH 177-191 inhibited lipogenesis in rat adipose tissue to the same degree as intact growth hormone but showed no significant lipolytic effect, measured as glycerol release from the fat pads of treated rats, which led the authors to place the hormone’s main effect on fat at the level of lipogenesis rather than lipolysis (Wu & Ng, Biochemistry and Molecular Biology International, 1993, 30(1):187–196). The same peptide reduced basal and insulin-stimulated glucose uptake in adipocytes isolated from obese Zucker rats, and was more potent than growth hormone at equal molar concentrations (Wijaya & Ng, Biochemistry and Molecular Biology International, 1993, 31(3):543–552).
• Lipolytic enzyme effects in later work — the 177-191 peptide (AOD9401) stimulated hormone-sensitive lipase and inhibited acetyl-CoA carboxylase in isolated rat adipose tissue and mimicked growth hormone’s effect on diacylglycerol release in adipocytes; 20 days of treatment in obese Zucker rats reduced weight gain and shrank mean adipocyte diameter from about 110 to 80 micrometers without the insulin resistance or glucose intolerance that growth hormone itself induced (Ng et al., Journal of Molecular Endocrinology, 2000, 25(3):287–298).
• A beta3-adrenergic receptor connection that is indirect — in obese mice, 14 days of intraperitoneal growth hormone or AOD9604 restored the suppressed expression of the beta3-adrenergic receptor, the main lipolytic receptor in fat cells, to lean-mouse levels. In beta3-receptor knockout mice, chronic treatment no longer produced weight loss or increased lipolysis, yet acute dosing still raised energy expenditure and fat oxidation, so the authors concluded the lipolytic action is not mediated directly through that receptor even though the peptide increases its expression (Heffernan et al., Endocrinology, 2001, 142(12):5182–5189).
• No binding to the growth hormone receptor — in BaF-BO3 cells transfected with the human growth hormone receptor, AOD9604 did not compete with radiolabeled growth hormone for binding and did not drive cell proliferation, while 14 days of infusion by mini-osmotic pump still reduced weight gain, raised fat oxidation and increased plasma glycerol in obese mice without the hyperglycemia seen with the full hormone (Heffernan et al., International Journal of Obesity, 2001, 25(10):1442–1449). Which receptor the fragment does act through has never been identified.

Research status

Early fragment pharmacology (1978–1982). The C-terminal region entered the literature as an insulin antagonist, not a fat-loss agent. Ng and Bornstein synthesized hGH 172-191, 176-191, 177-191, 178-191, 179-191 and 180-191 and dosed normal rats: the four longer peptides, 176-191 among them, produced a short-lived rise in blood glucose and a more sustained rise in plasma insulin, and peptides containing the 178-191 sequence reduced insulin sensitivity in intravenous insulin tolerance tests (American Journal of Physiology, 1978, 234(5):E521–E526). Chain-shortening studies on a ring-opened, carbamidomethylated 177-191 peptide then placed the insulin-antagonistic core within residues 178 to 190 (Wade et al., Acta Endocrinologica, 1982, 101(1):10–14).

Antilipogenic and anti-obesity work in rodents (1993–2001). The two 1993 adipose-tissue papers above were followed by a chronic study in which hGH 177-191 reduced cumulative body weight gain and adipose tissue mass in ob/ob mice, with lipogenesis in fat significantly inhibited (Natera et al., Biochemistry and Molecular Biology International, 1994, 33(5):1011–1021). Oral AOD9401 given to ob/ob mice for 30 days lowered weight gain from day 16 onward without changing food intake, reduced lipogenic and increased lipolytic activity in excised fat, acutely raised energy expenditure and fat oxidation, and in vitro increased lipolysis and decreased lipogenesis in adipose tissue from obese rodents and from humans (Heffernan et al., American Journal of Physiology-Endocrinology and Metabolism, 2000, 279(3):E501–E507). Two-dimensional NMR of the cyclic 177-191 peptide showed two type I beta-turns in its cyclic region and some resemblance to the same residues in the crystal structure of intact growth hormone (Ogru et al., Journal of Peptide Research, 2000, 56(6):388–397). For the tyrosine analog, 19 days of oral AOD9604 at 500 micrograms per kilogram cut weight gain in obese Zucker rats by more than half relative to controls, increased adipose lipolytic activity, and showed no adverse effect on insulin sensitivity under euglycemic clamp (Ng et al., Hormone Research, 2000, 53(6):274–278); the two 2001 Heffernan papers in Endocrinology and the International Journal of Obesity completed the rodent record.

Human trials: none for the unmodified fragment; a failed program for the analog. No clinical study of hGH 176-191 or 177-191 in humans has been published, and as of November 3, 2026 ClinicalTrials.gov lists no study of either the fragment or AOD-9604. The human data that circulate under the fragment’s name belong to AOD-9604. Metabolic Pharmaceuticals ran six trials between 2001 and 2006 (METAOD001 through METAOD006), summarized by company-affiliated authors in Stier, Vos and Kenley, Journal of Endocrinology and Metabolism, 2013, 3(1-2):7–15: two intravenous single-dose studies in 15 healthy men and 23 men with obesity, two short oral studies in 17 and 36 men with obesity, a 12-week oral study in 300 adults with obesity reported only as a 2005 meeting abstract, and the 24-week Phase 2b OPTIONS study, registered on the Australian New Zealand Clinical Trials Registry as ACTRN12605000067673 on August 2, 2005. OPTIONS enrolled 536 and randomized 502 adults with obesity to oral AOD-9604 or placebo alongside a supervised diet and exercise program; weight loss versus placebo at the 12-week primary endpoint and the 24-week secondary endpoint was too small to reach statistical significance, and on February 21, 2007 the company announced that the results did not support commercial viability and that development for obesity was terminated. The pivotal results were never published in a peer-reviewed journal. The FDA’s 2024 review of these summaries concluded that, in most of the studies it identified, AOD-9604 failed to show benefit for weight reduction compared with placebo.

Peripheral recent work. A 2022 in vitro study loaded a peptide labeled “hGH fragment 176-191” with doxorubicin into chitosan nanoparticles and reported greater antiproliferative activity against MCF-7 breast cancer cells than doxorubicin-loaded particles alone (Habibullah et al., Drug Design, Development and Therapy, 2022, 16:1963–1974); it is a drug-delivery experiment, not metabolic research, and did not test the fragment as a treatment on its own. Anti-doping laboratories have characterized AOD-9604’s detection in urine and identified the ring-containing metabolite CRSVEGSCG as more stable in serum than the parent peptide (Cox et al., Drug Testing and Analysis, 2015, 7(1):31–38); that metabolite sequence lies within the native fragment as well. Narrative reviews published in 2026 still list the compound only among research-market peptides lacking human efficacy data.

Common dosage forms

• Research market — lyophilized powder in vials, most commonly labeled 2 mg or 5 mg. The sequence inside such a vial is whatever the vendor’s certificate says it is; some products sold as “Frag 176-191” carry the native phenylalanine-176 sequence and others carry the tyrosine-substituted AOD-9604 sequence.
• No pharmaceutical presentation — there is no approved product, pen, tablet, capsule or spray containing the unmodified fragment in any country.
• Compounded presentations are of the analog — the AOD-9604 products described in the FDA’s 2024 review (a 1,200 mcg/mL subcutaneous injection, a 600 mcg oral capsule and a 600 mcg/g topical cream in the compounding nominations, and 250 mcg orally disintegrating tablets, 1 mg capsules and 600 to 1,000 mcg/mL injection vials marketed by US clinics) contained AOD-9604, not the native fragment.

Key considerations

• Not approved anywhere, and the closest analog was reviewed and advised against. The native fragment has never been nominated for the FDA’s 503A compounding list or evaluated by any regulator. Its analog AOD-9604 was placed in 503A Category 2 (significant safety concerns) on September 29, 2023, removed from the category list in September 2024 after the nominators withdrew, and then reviewed anyway at the FDA’s own initiative: on December 4, 2024 the Pharmacy Compounding Advisory Committee voted 0 to 12 against placing AOD-9604 free base or acetate on the bulks list, and the FDA’s category list updated May 14, 2026 does not carry AOD-9604 in any category. The Research Market status reflects the absence of any US approval, any registered clinical trial, and any active development program for the unmodified fragment.
• The human evidence is zero for this molecule and negative for its analog. Every efficacy claim rests on rodent and ex vivo work from 1993 to 2001, nearly all from a single Monash group whose peptide Metabolic Pharmaceuticals took into development. The one human program that tested the concept, in roughly 900 participants across six trials, ended with a 24-week Phase 2b failure on its primary weight-loss endpoint. Nothing published since has revisited the fragment in people.
• Safety signals point in two directions. The native 176-191 sequence raised blood glucose and plasma insulin and reduced insulin sensitivity in normal rats in the 1978 study, which is the opposite of the “no diabetogenic effect” that later rodent work reported for the 177-191 peptide and AOD-9604; whether the single Phe-to-Tyr change explains the difference is unknown. In the AOD-9604 trials the most common adverse events were headache, diarrhea and flatulence at oral doses and headache, fatigue, chest tightness and euphoria after intravenous doses; serious adverse events among the 300 participants in the 12-week study were four cancers (basal cell carcinoma, squamous cell carcinoma, breast cancer and malignant melanoma) and a benign lipoma, which the investigators judged unrelated and which the FDA review found the published information insufficient to confirm. The native fragment has no human safety data at all.
• Three names, one 16-residue span. “hGH 176-191” is the native sequence beginning with phenylalanine; “hGH 177-191” and AOD9401 are the 15-residue version without that first residue; AOD-9604 is 177-191 with a tyrosine added at the amino terminus. Product listings, review articles and anti-doping papers use 176-191 and 177-191 interchangeably, so identity should be checked by sequence rather than by name.
• Prohibited in sport. The World Anti-Doping Agency has listed growth hormone fragments under section S2, prohibited at all times, since the 2018 Prohibited List, naming AOD-9604 and hGH 176-191 as its examples; the 2026 list, in force since January 1, 2026, retains that wording at S2.2.3, and validated urine assays for the shared CRSVEGSCG metabolite exist.