Retatrutide
About
Retatrutide, developed by Eli Lilly and also known as LY3437943, is a synthetic peptide that acts as a triple receptor agonist at the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCG) receptors. GLP-1 and GIP are incretin hormones that stimulate insulin secretion, while glucagon-receptor activation is thought to increase metabolic rate and energy expenditure. Research has explored this triple mechanism for glycemic control and weight loss, with findings largely from clinical trials still in progress.
Research Applications
- Weight loss
- Glycemic control
- Metabolic rate and energy expenditure
Mechanism of Action
Retatrutide combines the effects of native GIP and GLP-1 with glucagon-receptor activation, producing a broad appetite-suppressing and metabolic effect that researchers suggest may differ from incretin-based therapies that act on fewer receptors.
Molecular Info
- Class
- Peptide
- Developer
- Eli Lilly (development code LY3437943)
- Mechanism
- Triple agonist of GIP, GLP-1, and glucagon receptors
- Primary research areas
- Weight loss, glycemic control, and metabolism
Dosing Guidance
- Range
- Research protocols describe an escalating once-weekly schedule starting at 1 mg and increasing to a maximum of 12 mg weekly.
- Frequency
- Once-weekly subcutaneous administration with gradual escalation in the cited protocols.
- Timing
- Timing is not consistently defined across the available research references.
- Cycle length
- Cycle length is not consistently defined across the available research references.
- Notes
- These details are educational context only. Protocol values are examples and should not be treated as medical instructions.
Known Risks
- Gastrointestinal issues reported in trials
- Reports of pancreatitis
- Hypersensitivity reactions
Regulatory & Evidence Status
- Evidence level
- Investigational; evidence comes from clinical trials still in progress, and long-term safety is not established.
- FDA status
- Not approved; under clinical investigation.
References
The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update
Endocrinology and Metabolism · 2024
DOI: 10.3803/EnM.2024.1942
Unleashing the power of retatrutide: A possible triumph over obesity and overweight: A correspondence
Health Science Reports · 2024
DOI: 10.1002/hsr2.1864
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: 10.1016/j.cmet.2022.07.013
Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity?
Expert Opinion on Investigational Drugs · 2023
DOI: 10.1080/13543784.2023.2206560
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: 10.1016/S0140-6736(23)01053-X
Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial
New England Journal of Medicine · 2023
DOI: 10.1056/NEJMoa2301972
GIPR Function in the Central Nervous System: Implications and Novel Perspectives for GIP-Based Therapies in Treating Metabolic Disorders
Diabetes · 2021
DOI: 10.2337/dbi21-0002
Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight
Journal of Clinical Investigation · 2014
DOI: 10.1172/JCI78371
Effects of GLP-1 and Incretin-Based Therapies on Gastrointestinal Motor Function
Experimental Diabetes Research · 2011
DOI: 10.1155/2011/279530
Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?
Frontiers in Endocrinology · 2022
DOI: 10.3389/fendo.2022.868037
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
The Lancet · 2022
DOI: 10.1016/S0140-6736(22)02033-5
The tolerance and safety of intravenously administered benzyl alcohol in methylprednisolone sodium succinate formulations in normal human subjects
Toxicology and Applied Pharmacology · 1972
DOI: 10.1016/0041-008x(72)90203-7
FDA Green-Lights Tirzepatide, Marketed as Zepbound, for Chronic Weight Management
JAMA · 2023
DOI: 10.1001/jama.2023.24539
What is the pipeline for future medications for obesity?
International Journal of Obesity · 2025
DOI: 10.1038/s41366-024-01473-y
For research and educational purposes only. Not medical advice. Consult a qualified healthcare professional before using any peptide. All calculations should be independently verified.
