Retatrutide molecular structure
Retatrutide molecular structure
Clinical Trial
🏋️Weight Loss

Retatrutide

Also known as: LY3437943, Reta, GGG Triple Agonist

MW

4703.40 Da

CAS

2381089-83-2

Routes

1 route

Retatrutide is a first-in-class triple incretin receptor agonist developed by Eli Lilly that simultaneously activates GIP, GLP-1, and glucagon receptors. By adding glucagon receptor agonism to the dual GIP/GLP-1 approach of tirzepatide, retatrutide produces the most pronounced weight loss observed for any anti-obesity medication in clinical trials — up to 24.2% body weight reduction at 48 weeks. The glucagon receptor component enhances energy expenditure through hepatic thermogenesis, lipolysis, and amino acid catabolism, while the GIP and GLP-1 components provide appetite suppression, insulin potentiation, and metabolic improvement. This triple mechanism addresses obesity from both the energy intake and energy expenditure sides.

Research Use Only— For educational and research purposes only

Research Applications

Obesity

Phase 2 trial demonstrated up to 24.2% body weight loss at 48 weeks (highest dose). Phase 3 TRIUMPH program ongoing.

Type 2 Diabetes

HbA1c reductions up to 2.0%. Phase 3 trials in progress.

MASH/NASH

Glucagon-mediated hepatic fat reduction makes retatrutide promising for NASH. Early data shows significant liver fat reduction.

Obstructive Sleep Apnea

Being studied based on weight loss efficacy and potential direct metabolic effects.

Mechanism of Action

Triple Incretin Receptor Agonism

Retatrutide activates three complementary metabolic hormone receptors: GLP-1R (appetite suppression, insulin secretion), GIPR (metabolic improvement, adipose function), and GCGR (glucagon receptor — enhanced energy expenditure, hepatic fat oxidation, thermogenesis). The glucagon component is the key differentiator from tirzepatide.

Glucagon-Mediated Energy Expenditure

Glucagon receptor activation in the liver drives glycogenolysis, gluconeogenesis, amino acid catabolism, and hepatic thermogenesis. It increases energy expenditure by 10-15% through enhanced fatty acid oxidation and ketogenesis — counteracting the metabolic adaptation (reduced energy expenditure) that typically limits weight loss durability.

Biological Pathways

GLP-1R/cAMP for appetite and insulin. GIPR/cAMP for adipose function. GCGR/cAMP/PKA/CREB for hepatic fat oxidation and energy expenditure. FGF21 upregulation via glucagon signaling. AMPK activation in liver and brown adipose tissue.

Dosage Information

Typical dosage ranges for research applications. Always verify with current literature.
Typical Dose
12,000 mcg
Dose Range
1,000 - 12,000 mcg
Frequency
Once weekly; titrate from 1 mg over ~16 weeks
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Calculation Results

Concentration
2.5 mg/ml
Dose Volume
0.1 ml0.100 ml
Insulin Syringe
10 units
Doses per Vial
2020 doses @ 250 mcg

Syringe Fill Level (100u syringe)

05010010.0uunits
0u10.0 / 100 units (10%)100u

Protocols

No protocols featuring this peptide yet.

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Stability & Storage

Retatrutide is in clinical development as a once-weekly subcutaneous injection. As an investigational compound, commercial stability data is not yet public. The C20 fatty acid chain enables albumin binding and once-weekly dosing through extended half-life.

Side Effects & Precautions

GI effects (nausea 16-25%, diarrhea 16-22%, vomiting 8-13%) are the most common, mitigated by slow dose titration. Decreased appetite. Transient heart rate increase. As the glucagon component theoretically opposes insulin's glucose-lowering effect, hyperglycemia is monitored but balanced by GLP-1/GIP components. Full safety profile pending Phase 3 data.

Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.

Regulatory Status

Clinical Trial

Investigational — Phase 3 clinical trials ongoing (TRIUMPH program). Not yet FDA-approved. Expected regulatory filings pending Phase 3 results. WADA-prohibited under S2.

Research Studies

Retatrutide Phase 2 Trial for Obesity

Jastreboff AM, Kaplan LM, Frías JP, et al.

New England Journal of Medicine
2023
View Source

Retatrutide Phase 2 for Type 2 Diabetes

Rosenstock J, Frias JP, Jastreboff AM, et al.

Lancet
2023
View Source

Triple Agonism of GIP/GLP-1/Glucagon Receptors

Finan B, Yang B, Ottaway N, et al.

Nature Medicine
2015
View Source
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