What Is Retatrutide? The Triple-Agonist Peptide Explained
By UK Peptide Lab Research Team•8 October 2026•7 min read
Key Takeaways
- Retatrutide (development code LY3437943) is an investigational synthetic peptide developed by Eli Lilly that acts as an agonist at three receptors: GIP, GLP-1 and glucagon.
- Published phase 2 trials in obesity and type 2 diabetes reported large reductions in body weight and HbA1c over 36 to 48 weeks, alongside dose-dependent gastrointestinal adverse events.
- It is not approved as a medicine in the UK, EU or US. This article is educational and is not medical advice or an offer to supply.
What is retatrutide?
Retatrutide is a synthetic peptide of roughly 39 amino acids, modified with a fatty diacid side chain that lets it bind albumin and stay in circulation for days rather than minutes. It was developed by Eli Lilly under the code LY3437943 and is the first agent in its class to target three incretin-axis receptors at once: the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor.
The name follows the usual convention for this family. Semaglutide acts on one receptor (GLP-1), tirzepatide on two (GIP and GLP-1), and retatrutide adds glucagon receptor activity on top, which is why it is often called a triple agonist.
How it works
GLP-1 receptor activation slows gastric emptying, increases glucose-dependent insulin secretion and acts on appetite circuits in the brain. GIP receptor activation contributes to insulin secretion and is thought to modulate how well the gastrointestinal effects of GLP-1 are tolerated. The addition of glucagon receptor agonism is the distinguishing feature: in preclinical and early clinical work, glucagon signalling was associated with increased energy expenditure and changes in hepatic lipid handling, which is why liver fat has been a prominent secondary endpoint.
The original characterisation in Cell Metabolism (Coskun et al., 2022) described a peptide with balanced but not equal potency across the three receptors, designed so that the glucagon component adds metabolic effect without driving blood glucose up, since the GLP-1 and GIP components offset it.
What the published trials report
Two phase 2 trials have been published in peer-reviewed journals. In the obesity trial (Jastreboff et al., New England Journal of Medicine, 2023), adults without diabetes were randomised to weekly retatrutide or placebo for 48 weeks. At the highest dose arm, mean body weight fell by about 24% from baseline, compared with about 2% on placebo, and weight had not plateaued when treatment ended.
In the type 2 diabetes trial (Rosenstock et al., The Lancet, 2023), participants were followed for 36 weeks. Retatrutide lowered HbA1c and body weight substantially more than placebo, and the highest dose arm outperformed the dulaglutide comparator on both measures.
In both studies the most common adverse events were gastrointestinal: nausea, diarrhoea, vomiting and constipation, mostly mild to moderate and clustered around dose escalation. Dose-dependent increases in heart rate were also reported. Phase 3 programmes are ongoing, so long-term safety and efficacy data are not yet complete.
Regulatory status in the UK
Retatrutide has not been granted a marketing authorisation by the MHRA, the European Medicines Agency or the US FDA. It is an investigational medicine, available only to participants in clinical trials. Any product marketed for human use outside of those trials is unlicensed. Material sold for laboratory research is not a medicine, is not manufactured to pharmaceutical standards and must not be used in people or animals. For the general legal position on research peptides, see our guide on whether peptides are legal in the UK.
Why it matters to researchers
Retatrutide is a useful reference point because it shows how far multi-receptor design has moved the field. Questions that remain open include how much of the weight effect is driven by reduced intake versus increased expenditure, how the glucagon component affects the liver and cardiovascular system over years, and how tolerability can be improved. Those questions will be answered by the phase 3 trials and by independent academic work, not by anecdote. If you are new to the underlying chemistry, start with our introduction to what peptides are.
Disclaimer: This article is for research and educational purposes only. All information provided is not intended as medical advice. UK Peptide Lab products are not for human consumption and are sold strictly for laboratory research use only.
Frequently Asked Questions
What is retatrutide?
An investigational synthetic peptide from Eli Lilly (LY3437943) that activates the GIP, GLP-1 and glucagon receptors.
Is retatrutide approved in the UK?
No. It has no marketing authorisation from the MHRA, EMA or FDA and is only available within clinical trials.
How is retatrutide different from semaglutide and tirzepatide?
Semaglutide targets GLP-1 only and tirzepatide targets GIP and GLP-1. Retatrutide adds glucagon receptor activity as a third target.
What did the phase 2 trials find?
Large reductions in body weight and HbA1c over 36 to 48 weeks versus placebo, with mainly gastrointestinal side effects. See the references below for the full data.
References
- [1] Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial. New England Journal of Medicine (2023). View →
- [2] 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. The Lancet (2023). View →
- [3] 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). View →