Retatrutide

Retatrutide is an investigational once-weekly peptide that activates the GIP, GLP-1 and glucagon receptors. It is not FDA-approved; Eli Lilly plans a BLA submission in Q1 2027 after phase 3 results.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

Retatrutide is a synthetic peptide developed by Eli Lilly that acts on three hormone receptors involved in metabolism: the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor. It is often called a triple agonist or "triple-G" agonist. It builds on the dual agonist tirzepatide by adding glucagon receptor activity, which is thought to increase energy expenditure and affect liver fat.

A phase 2 obesity trial published in the New England Journal of Medicine in 2023 reported dose-dependent weight reduction compared with placebo. Retatrutide then entered the TRIUMPH phase 3 program. In July 2026 Lilly announced positive TRIUMPH results and said it plans to submit a biologics license application in the first quarter of 2027. Retatrutide is not approved by the FDA and FDA has stated it cannot be used in compounding.

Compare: Semaglutide vs Tirzepatide vs Retatrutide.

Structure

Retatrutide is a single linear peptide with a backbone derived from GIP and engineered to activate the GLP-1 and glucagon receptors as well. It includes non-natural residues such as α-aminoisobutyric acid to resist dipeptidyl peptidase-4 cleavage and a lysine side chain linked to a fatty diacid that promotes reversible albumin binding, supporting once-weekly dosing. The C-terminus is amidated.

Mechanism

Retatrutide is an agonist at the GIP, GLP-1 and glucagon receptors. It has been described as having greater relative potency at the GIP receptor and lower relative potency at the GLP-1 and glucagon receptors compared with the native hormones. GLP-1 and GIP receptor activation contribute to glucose-dependent insulin secretion and reduced appetite.

Glucagon receptor activation is proposed to increase energy expenditure and promote fat oxidation in the liver, which may add to weight and liver fat effects beyond those of dual agonists. Glucagon also raises blood glucose, which is thought to be offset by the incretin components. The relative contribution of each receptor to the observed effects in humans is not fully established.

Research

Phase 2 obesity trial

A randomized, placebo-controlled phase 2 trial in adults with obesity, published in 2023 by Jastreboff and colleagues, evaluated several doses of once-weekly retatrutide over 48 weeks. It reported dose-dependent reductions in body weight that were substantially greater than placebo. Gastrointestinal adverse events were the most common, and heart rate increases were observed. These results supported progression to phase 3. The trial was published by Jastreboff and colleagues in the New England Journal of Medicine.

TRIUMPH phase 3 program

The TRIUMPH program is Lilly's phase 3 clinical development program for retatrutide, studying adults with obesity or overweight, including those with type 2 diabetes and other weight-related conditions. In July 2026 Lilly announced positive phase 3 results and stated plans to submit a BLA in Q1 2027. Full peer-reviewed publication of all TRIUMPH results should be consulted for details as it becomes available.

Type 2 diabetes and liver fat

Separate phase 2 studies examined retatrutide in people with type 2 diabetes, measuring glycemic control and body weight, and substudies assessed liver fat by imaging. Reductions in liver fat were reported, which is consistent with the proposed role of glucagon receptor activation. These are mid-stage clinical findings, and outcomes for liver disease have not been established in phase 3. Longer studies will be needed to define effects on liver outcomes.

Regulatory status

Retatrutide is investigational and not approved by the FDA or other major regulators. On July 23, 2026, Eli Lilly said it plans to submit a biologics license application in Q1 2027 following positive TRIUMPH phase 3 results. FDA has stated that retatrutide cannot be used in pharmacy compounding. For its status in sport, check the current WADA Prohibited List.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

A COA should confirm identity by mass spectrometry, with the observed mass matching the expected mass for the acylated peptide shown on this page, and report purity by reverse-phase HPLC. Because the compound is investigational, published reference standards and pharmacopeial methods are not available, which makes independent identity confirmation especially important. Key impurities include non-acylated peptide, incomplete side chains, deletion sequences and racemized residues; confusion with other incretin peptides of similar length should be excluded by mass. Aggregation, endotoxin and net peptide content should be reported.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store lyophilized retatrutide sealed at -20 °C, protected from light and moisture. As an acylated, amphiphilic peptide, it can self-associate or aggregate in solution, so avoid vigorous shaking and choose buffers suited to the application. Reconstituted laboratory solutions should be refrigerated, used promptly and aliquoted to avoid repeated freeze-thaw cycles.

Download the Retatrutide data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• Tirzepatide

  Tirzepatide is a once-weekly peptide that activates both the GIP and GLP-1 receptors. It is FDA-approved for type 2 diabetes (Mounjaro) and chronic weight management (Zepbound).

• Semaglutide

  Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. It is FDA-approved for type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy).

• Cagrilintide

  Cagrilintide is an investigational long-acting acylated analogue of amylin, a pancreatic hormone involved in satiety. It has been studied alone and in combination with semaglutide (CagriSema) for weight management.

References

1. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med. 2023. Find on PubMed
2. PubMed: all indexed literature on Retatrutide
3. ClinicalTrials.gov: registered studies mentioning Retatrutide