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The science, from the published literature

Plain-English summaries of published research on retatrutide and GHK-Cu, with links to the original papers.

Retatrutide · GHK-Cu

Important. Our products are for laboratory research use only and are not for human or veterinary consumption. This page summarises published scientific literature for information only. It is not medical advice, and nothing here suggests our products are safe or suitable for any use in people. Our products are not approved therapeutic goods. For laboratory research use only. Not for human or veterinary use.

Retatrutide

What it is

Retatrutide (development code LY3437943) is a single synthetic peptide developed by Eli Lilly. It belongs to a class researchers call "triple agonists": one molecule designed to activate three different hormone receptors, the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor [1]. Earlier compounds in this field act on one receptor (GLP-1) or two (GIP and GLP-1).

Diagram: one retatrutide molecule binds three receptors: GIP, GLP-1 and glucagon Retatrutide GIP receptor GLP-1 receptor Glucagon receptor
One peptide, three receptor targets (simplified).

How it works

GIP, GLP-1 and glucagon are natural gut and pancreatic hormones involved in regulating blood sugar, appetite and energy use. Each acts through its own receptor on the surface of cells. When a hormone (or a molecule that mimics it) binds its receptor, the receptor switches on signalling inside the cell.

  • GLP-1 receptor: involved in glucose-dependent insulin release, slowed stomach emptying and appetite signalling in the brain.
  • GIP receptor: also involved in glucose-dependent insulin release, and studied for its effects on fat tissue.
  • Glucagon receptor: mainly in the liver, where glucagon raises glucose output; it is also studied for its effects on energy expenditure and liver fat.

In its preclinical and early clinical characterisation, retatrutide was reported to be more potent at the human glucagon and GLP-1 receptors relative to their native hormones than at the GIP receptor, and in animal studies the glucagon activity was associated with increased energy expenditure [1]. Researchers' working idea is that combining the three signals produces effects that no single pathway does.

What the trials observed over time

In the phase 2 obesity trial, participants were assigned to retatrutide or placebo for 48 weeks, and in most retatrutide groups doses were increased gradually rather than started at the full level [2]. In the highest-dose group, mean body weight had fallen 17.5% at 24 weeks and 24.2% at 48 weeks, compared with 1.6% and 2.1% in the placebo group, so average weight was still decreasing between the two time points [2]. At 48 weeks, 83% of participants in that group had lost 15% or more of their body weight, compared with 2% on placebo [2].

The most common adverse events in the retatrutide groups were gastrointestinal. They were dose-related, mostly mild to moderate, and partly reduced when a lower starting dose was used [2]. In the phase 2 type 2 diabetes trial, mild-to-moderate gastrointestinal events, including nausea, diarrhoea, vomiting and constipation, were reported in 35% of retatrutide participants, compared with 13% on placebo [3]. In the obesity trial, heart rate rose in a dose-dependent way, peaked at 24 weeks and declined after that [2].

These are group averages from controlled clinical trials conducted under medical supervision, and they do not predict outcomes for any individual.

Key published research

  • 2022, preclinical and phase 1 (Cell Metabolism). Coskun et al. described the design of LY3437943 and reported results in mice and an early single-dose study in healthy people [1].
  • 2023, phase 2 in obesity (NEJM). Jastreboff et al. ran a 48-week, double-blind, placebo-controlled trial in 338 adults with obesity or overweight. In the highest-dose group, mean body weight fell 24.2% at 48 weeks, compared with 2.1% in the placebo group. The most common side effects were gastrointestinal [2].
  • 2023, phase 2 in type 2 diabetes (The Lancet). Rosenstock et al. randomised 281 adults with type 2 diabetes. At 24 weeks, HbA1c fell by up to 2.02 percentage points in retatrutide groups, versus 0.01 with placebo and 1.41 with the comparator dulaglutide [3].
  • 2025–2026, phase 3 TRIUMPH program. Eli Lilly has reported topline results from several phase 3 trials. In TRIUMPH-4 (obesity with knee osteoarthritis, 68 weeks) mean weight change was up to −28.7% versus −2.1% with placebo [4]. In TRIUMPH-1 (obesity without diabetes, 80 weeks) it was up to −28.3% [5]. TRIUMPH-2 (obesity with type 2 diabetes) has been published in The Lancet, and TRIUMPH-3 (severe obesity with cardiovascular disease) reported up to −22.6% versus −3.2% with placebo [6][7]. Several of these are company-reported topline results that have not yet all been published in full peer-reviewed form.

Research status

Retatrutide is an investigational compound. As at October 2026 it has not been approved by the U.S. FDA or the Australian TGA for any use. Lilly has said it plans to submit an application to the FDA in the first quarter of 2027 [6]. Trial results describe outcomes in supervised clinical studies and do not apply to research materials.

References

  1. Coskun T, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metabolism. 2022. doi.org/10.1016/j.cmet.2022.07.013
  2. Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med. 2023. doi.org/10.1056/NEJMoa2301972
  3. Rosenstock J, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. The Lancet. 2023. doi.org/10.1016/S0140-6736(23)01053-X
  4. Eli Lilly and Company. TRIUMPH-4 topline results (press release). 11 December 2025. investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average
  5. Eli Lilly and Company. TRIUMPH-1 topline results (press release). 21 May 2026. investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss
  6. Eli Lilly and Company. TRIUMPH-2 and TRIUMPH-3 topline results (press release). 23 July 2026. www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html
  7. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. The Lancet. 2026. www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01861-1/abstract

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GHK-Cu

What it is

GHK-Cu is a copper complex of the tripeptide glycyl-L-histidyl-L-lysine (GHK): three amino acids, glycine, histidine and lysine, with a copper(II) ion bound to the peptide. GHK occurs naturally in human plasma, saliva and urine. It was identified in human plasma by Loren Pickart and colleagues in the early 1970s [1][4]. GHK has a strong affinity for copper, and much of the research focuses on the copper-bound form. GHK-Cu is one component of our GLOW blend.

Diagram: the tripeptide glycine-histidine-lysine bound to a copper ion Gly His Lys Cu²⁺
GHK tripeptide with bound copper (simplified, not to scale).

How it works

Unlike retatrutide, GHK-Cu is not known to act through one specific receptor. Researchers have described several overlapping mechanisms:

  • Copper transport: GHK binds copper and may deliver it to cells, and copper is needed by enzymes such as lysyl oxidase that help build connective tissue [4].
  • Extracellular matrix signalling: in cell culture, GHK-Cu increased production of collagen and other matrix components by fibroblasts [2].
  • Gene expression: analyses of public gene-expression data (the Broad Institute's Connectivity Map) suggest GHK shifts the activity of a large number of human genes, including genes linked to tissue remodelling and antioxidant responses [4][6].

Key published research

  • 1973, in vitro (Biochemical and Biophysical Research Communications). Pickart and colleagues reported that a synthetic version of the plasma tripeptide increased survival of normal liver cells in culture [1].
  • 1988, in vitro (FEBS Letters). Maquart et al. reported that GHK-Cu stimulated collagen synthesis in cultured fibroblasts [2].
  • 1993, animal (Journal of Clinical Investigation). Maquart et al. reported increased connective tissue accumulation when GHK-Cu was applied to experimental wound chambers in rats [3].
  • 2012, gene expression (Genome Medicine). Campbell et al. identified a gene-expression signature of emphysema-related lung damage, then used the Connectivity Map to find compounds predicted to reverse it. GHK was one; in cultured lung fibroblasts from people with COPD, GHK was reported to restore aspects of normal tissue-repair behaviour [5].
  • 2015 and 2018, reviews. Pickart and colleagues reviewed the body of research on GHK, covering laboratory, animal and small human cosmetic studies, and the gene-expression data [4][6]. Their reviews are a useful starting point, but note that the lead author discovered the compound.

What kind of evidence is it?

Most GHK-Cu research is in vitro (cells in a dish) or in animals. Human data come mainly from small cosmetic studies of topical products, which reviews summarise but which were generally not large, independent, placebo-controlled trials. There are no large modern clinical trials of GHK-Cu comparable to the retatrutide program.

Research status

GHK-Cu is used as an ingredient in some cosmetic products. It is not an approved medicine in Australia, and our GHK-Cu-containing product is supplied for laboratory research only.

References

  1. Pickart L, Thayer L, Thaler MM. A synthetic tripeptide which increases survival of normal liver cells, and stimulates growth in hepatoma cells. Biochem Biophys Res Commun. 1973;54:562–566. doi.org/10.1016/0006-291X(73)91459-9
  2. Maquart FX, et al. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Letters. 1988. doi.org/10.1016/0014-5793(88)80509-X
  3. Maquart FX, et al. In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds. J Clin Invest. 1993. doi.org/10.1172/JCI116842
  4. Pickart L, Vasquez-Soltero JM, Margolina A. GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration. BioMed Research International. 2015. doi.org/10.1155/2015/648108
  5. Campbell JD, et al. A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK. Genome Medicine. 2012. doi.org/10.1186/gm367
  6. Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. Int J Mol Sci. 2018. doi.org/10.3390/ijms19071987

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