What is Retatrutide?

Introduction:

Retatrutide is a synthetic research peptide classified as a triple-agonist — it activates the GLP-1, GIP, and glucagon receptors.¹ This unique profile distinguishes it from semaglutide (GLP-1 agonist) and tirzepatide (dual GLP-1/GIP agonist). Retatrutide has attracted attention in research for its potential role in weight management, glucose regulation, and metabolic health.
For research use only — not for human consumption.

Discovery & Background

Retatrutide (also known as LY3437943) was developed by Eli Lilly as part of its next-generation incretin program.² Its design combines activity across three key hormonal pathways:

GLP-1 (Glucagon-like peptide-1): Stimulates insulin secretion, slows gastric emptying, reduces appetite.
GIP (Glucose-dependent insulinotropic polypeptide): Enhances insulin sensitivity and lipid metabolism.
Glucagon receptor: Increases energy expenditure and fat metabolism.³

Early trials suggest that combining all three pathways may produce greater metabolic benefits than GLP-1 or GLP-1/GIP agonists alone.

Research Applications

Retatrutide has been studied primarily in the context of:

Obesity research: Trials show participants lost over 24% of body weight at high doses — exceeding results seen with semaglutide or tirzepatide.⁴
Diabetes research: Demonstrated strong glucose-lowering effects in early studies.
Metabolic health: Potential effects on lipid metabolism, fatty liver, and cardiometabolic risk factors.

Insert Figure 1: Diagram comparing GLP-1, GLP-1/GIP, and GLP-1/GIP/Glucagon pathways.
ALT: “Diagram showing receptor targets of semaglutide (GLP-1), tirzepatide (GLP-1/GIP), and retatrutide (GLP-1/GIP/glucagon).”
Caption: “Figure 1. Retatrutide’s triple agonist design expands incretin research into three hormonal pathways.”

Key Differences from Other Incretin Peptides

Versus Semaglutide: Retatrutide adds both GIP and glucagon receptor activity, potentially producing greater weight loss.
Versus Tirzepatide: Retatrutide adds glucagon receptor activation, which may further enhance fat metabolism and energy expenditure.
Versus Both: Retatrutide is still in early-stage trials, whereas semaglutide and tirzepatide have larger research datasets.

Limitations of Current Research

Early-stage evidence: Most data comes from Phase 2 trials.⁵
Safety profile: GI side effects are expected, but long-term safety remains unconfirmed.
Not yet as studied: Compared to semaglutide and tirzepatide, retatrutide research is less mature.

Summary

Retatrutide is a triple incretin receptor agonist peptide studied for its effects on weight loss, glucose regulation, and metabolic health. Early evidence suggests it may surpass semaglutide and tirzepatide in weight reduction, but its long-term safety and efficacy remain under investigation.

FAQs About Retatrutide