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Research Reference · Metabolic & Weight-Loss Research

Retatrutide

An investigational once-weekly peptide (LY3437943) that activates three receptors — GLP-1, GIP and glucagon — studied in weight-loss (obesity), diabetes and fatty-liver research.

Last reviewed September 2026 8 peer-reviewed sources 3-minute read

At a glance

Retatrutide (LY3437943) is an investigational peptide from Eli Lilly that activates three hormone receptors at once: GLP-1, GIP and glucagon. It is one of the most closely watched molecules in obesity and metabolic research, with phase 2 trials published in weight loss, type 2 diabetes and fatty liver, and a phase 3 programme under way. It is not an approved drug.

TypeTriple-agonist peptide
Studied forObesity, diabetes & liver fat
Evidence stagePhase 2 trials published
Human dataRandomized trials; not approved

What it’s studied for

Weight-loss (obesity) research

Substantial, dose-related weight reductions over 48 weeks in adults with obesity. 2

Human · phase 2

Blood-sugar control

Improved glycaemic control and weight in type 2 diabetes versus placebo and dulaglutide. 3

Human · phase 2

Liver fat

Large reductions in liver fat, with most participants at the higher doses reaching normal levels by 24 weeks. 4

Human · phase 2a

Energy expenditure

The glucagon component adds higher energy expenditure to the reduced food intake driven by GIP and GLP-1. 1

Animal & human

Retatrutide

From $74.99 · 10 mg · 15 mg · 20 mg · 30 mg · 50 mg

Third-party tested · batch-matched COA · research use only

View Retatrutide Retatrutide COAsUsage guide

How it works

Retatrutide is a single peptide engineered to activate three receptors involved in appetite and metabolism: GLP-1 and GIP — the two targets of tirzepatide — plus the glucagon receptor. 1 In discovery work, the glucagon component added an increase in energy expenditure on top of the reduced food intake driven by GIP and GLP-1, and the molecule was designed to be long-acting. 1,5

In phase 2 trials it produced substantial, dose-related weight reductions over 48 weeks in adults with obesity, 2 improved blood-sugar control in type 2 diabetes, 3 and sharply cut liver fat in people with fatty liver disease. 4 It also slows gastric emptying. 6 The most common side effects were gastrointestinal, and heart rate rose early in treatment before declining. 2

Retatrutide is the reference triple agonist — compared against single-receptor (semaglutide) and dual-receptor (tirzepatide) molecules. 7,8

Related research

TirzepatideDual GIP/GLP-1 SemaglutideGLP-1 only Bioglutide (NA-931)Investigational oral agonist MOTS-cMetabolic research

Frequently asked questions

What is LY3437943?
The development code Eli Lilly used for retatrutide in its discovery and early clinical papers.
How is retatrutide different from tirzepatide?
Tirzepatide activates two receptors (GIP and GLP-1). Retatrutide adds a third, the glucagon receptor, which in discovery studies added higher energy expenditure.
Is retatrutide approved?
No. It is an investigational peptide; phase 2 results are published and a phase 3 programme is under way.
What have the trials found?
Phase 2 trials reported substantial weight reduction in obesity, better blood-sugar control in type 2 diabetes, and large reductions in liver fat. Gastrointestinal side effects were the most common.
What is the CAS number of retatrutide?
2381089-83-2.

Identifiers

Name Retatrutide
Development code LY3437943
Class GIP, GLP-1 and glucagon receptor triple agonist (peptide)
CAS number 2381089-83-2
UNII NOP2Y096GV
Status Investigational — not an approved drug
Supplied as Lyophilized (freeze-dried) powder

PubChem has no compound record for retatrutide; CAS and UNII checked against its public drug record. No molecular formula is listed because it could not be confirmed against a primary database.

Research timeline

  1. 2022Discovery paper: LY3437943 from design to clinical proof of concept 1; phase 1b trial in type 2 diabetes. 5
  2. 2023Phase 2 trials in obesity 2 and type 2 diabetes 3; gastric-emptying study. 6
  3. 2024Phase 2a trial shows large liver-fat reductions 4; review of the triple-agonist approach. 8
  4. 2025Review of retatrutide in obesity pharmacotherapy. 7

Key studies

StudyModelWhat it found
Coskun 2022 1 Animal + phase 1 Glucagon receptor adds energy expenditure; weight reduction persisted to day 43 after a single dose.
Urva 2022 5 Human · phase 1b Acceptable safety in type 2 diabetes; dose-dependent reductions in glucose and body weight.
Jastreboff 2023 2 Human · phase 2 Substantial weight reduction over 48 weeks; mostly mild-to-moderate GI side effects.
Rosenstock 2023 3 Human · phase 2 Better glycaemic control and weight reduction in type 2 diabetes; informed phase 3 dose selection.
Sanyal 2024 4 Human · phase 2a Liver fat fell by more than 80% at the higher doses; most reached normal liver fat at 24 weeks.

Sources

  1. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Coskun T, et al. Cell Metab, 2022.
  2. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. Jastreboff AM, et al. N Engl J Med, 2023. Human · phase 2
  3. 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. Rosenstock J, et al. Lancet, 2023. Human · phase 2
  4. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Sanyal AJ, et al. Nat Med, 2024. Free full textHuman · phase 2a
  5. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Urva S, et al. Lancet, 2022. Human · phase 1b
  6. The novel GIP, GLP-1 and glucagon receptor agonist retatrutide delays gastric emptying. Urva S, et al. Diabetes Obes Metab, 2023.
  7. Retatrutide-A Game Changer in Obesity Pharmacotherapy. Katsi V, et al. Biomolecules, 2025. Free full textReview
  8. The power of three: Retatrutide’s role in modern obesity and diabetes therapy. Abdul-Rahman T, et al. Eur J Pharmacol, 2024. Review
For Research Use Only. This page summarizes published scientific research for educational purposes. It is not medical advice and does not promote, recommend, or describe any human or animal use. Products referenced are sold strictly for laboratory research and are not for human consumption.

Last reviewed September 2026 by Midwest Compounds. Every source above was checked against its original publication.