Wiki · Profile

Retatrutide

LY3437943

Metabolic & WeightPhase III

MW: 4731g/mol
Formula: C221H342N46O68

Retatrutide is a novel peptide classified as a triple receptor agonist, targeting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors. Researchers primarily study retatrutide for its potential in managing obesity and type 2 diabetes mellitus (T2DM). Key findings from clinical trials indicate that retatrutide can induce significant weight loss of up to 26.56% in individuals with obesity, alongside notable reductions in glycated hemoglobin levels and improvements in metabolic parameters. Additionally, preclinical evidence suggests its mechanisms include delaying gastric emptying and reducing food intake. Current research is ongoing, with Phase III trials, such as the TRIUMPH studies, evaluating the long-term safety and efficacy of retatrutide in diverse patient populations.

Chemical Profile

Chemical Structure

Formula	C221H342N46O68
Molecular Weight	4731 g/mol
CAS Number	2381089-83-2
PubChem CID	171390338

Half-Life

SCSubcutaneous

Data limited

INIntranasal

Not applicable

POOral

Poor bioavailability

Retatrutide is primarily administered subcutaneously due to its peptide nature and poor oral bioavailability.

Mechanism

Mechanism of Action

Retatrutide is a triple receptor agonist that targets the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors, activating signaling pathways such as the cAMP/PKA pathway and the ERK1/2 pathway. This activation leads to delayed gastric emptying, reduced food intake, enhanced insulin secretion, and improved glycemic control, ultimately promoting significant weight loss and favorable metabolic outcomes. While the precise mechanisms underlying its effects on body composition and metabolic health are still being elucidated, its multifaceted action suggests a complex interplay of these signaling pathways in regulating appetite and energy homeostasis.

Research

77 Research Publications

3,757

Total Citations

Human/RCT

7.4

Avg. Influence

2026

Latest

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Filter

01Top

#01

Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.

Jastreboff Ania M, et al. · The New England journal of medicine · 2023

HumanInfluence103.0

765

The study demonstrated that retatrutide resulted in substantial weight reductions of up to 24.2% in humans with obesity after 48 weeks of treatment.

Key findings

01At 48 weeks, participants taking the highest dose of retatrutide lost an average of 24.2% of their body weight, while those on placebo lost only 2.1%.
02A large majority of participants on retatrutide achieved weight reductions of 5%, 10%, or 15%, with the highest rates in those receiving the 8 mg and 12 mg doses.
03The most common side effects were mild to moderate gastrointestinal issues, which were more frequent at higher doses.

1 mgsubcutaneous(human)48 weeks4 mgsubcutaneous(human)48 weeks8 mgsubcutaneous(human)48 weeks12 mgsubcutaneous(human)48 weeks4 mgsubcutaneous(human)40 weeks9 mgsubcutaneous(human)40 weeks12 mgsubcutaneous(human)40 weeks1 mgsubcutaneous(human)48 weeks4 mgsubcutaneous(human)48 weeks8 mgsubcutaneous(human)48 weeks12 mgsubcutaneous(human)48 weeks

PubMed

02Top

#02

Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity.

Drucker Daniel J · Diabetes care · 2024

ReviewInfluence15.0

327

The study demonstrated that GLP-1-based medicines, including retatrutide, show substantial efficacy for weight loss and improved metabolic outcomes in humans with obesity and type 2 diabetes.

Key findings

01Researchers observed that GLP-1 medicines provide significant benefits for heart and kidney health in certain patients.
02The study highlighted ongoing research into the use of GLP-1 medications for conditions like liver disease, Parkinson's, and Alzheimer's.
03Newer GLP-1-based drugs are being developed, which may offer different benefits and enhance personalized treatment strategies.

PubMed

03Top

#03

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 Julio, et al. · Lancet (London, England) · 2023

HumanInfluence41.0

309

Researchers observed that retatrutide significantly improved glycemic control and body weight in humans with type 2 diabetes compared to placebo and dulaglutide.

Key findings

01Retatrutide showed clinically meaningful improvements in blood sugar control in participants with type 2 diabetes.
02Participants experienced robust reductions in body weight while using retatrutide.
03The safety profile of retatrutide was consistent with other GLP-1 receptor agonists.

PubMed

#04

What is the pipeline for future medications for obesity?

Melson Eka, et al. · International journal of obesity (2005) · 2025

ReviewInfluence7.0

308

The review highlighted that combinations of GLP-1 with other hormones, including retatrutide, may enhance weight loss and cardiometabolic benefits compared to existing obesity treatments.

Key findings

01Researchers observed that the GLP-1 receptor agonist semaglutide can lead to a 15-17% average weight loss.
02The dual GLP-1/GIP receptor agonist tirzepatide showed even greater weight loss of up to 22.5% in trials.
03New combinations of gut hormones are being tested, with early results suggesting they may provide even better weight loss outcomes than current treatments.

PubMed

#05

Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.

Sanyal Arun J, et al. · Nature medicine · 2024

HumanInfluence24.0

284

The study demonstrated that retatrutide significantly reduced liver fat by up to 82.4% in humans with metabolic dysfunction-associated steatotic liver disease after 24 weeks.

Key findings

01Participants receiving retatrutide experienced liver fat reductions of up to 82.4%, while those on placebo saw no change.
02By the end of the study, a substantial percentage of participants on retatrutide achieved normal liver fat levels, with 86% in the highest dose group.
03The reduction in liver fat was closely linked to improvements in body weight and metabolic health indicators.

PubMed

#06

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 Tamer, et al. · Cell metabolism · 2022

HumanInfluence11.0

214

Researchers studied a new medication called LY3437943, which targets three receptors to help manage weight and blood sugar levels. They found that this treatment led to weight loss and improved blood sugar control in obese mice, and showed a good safety profile in early human trials.

Key findings

01LY3437943 decreased body weight and improved glycemic control in obese mice.
02The medication increased energy expenditure while reducing calorie intake.
03In a phase 1 human trial, LY3437943 demonstrated a safety profile similar to existing treatments and effects lasted for up to 43 days after a single dose.

PubMed

#07

Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?

Locatelli João Carlos, et al. · Diabetes care · 2024

ReviewInfluence4.0

149

Researchers observed that retatrutide, in combination with resistance exercise, may optimize body composition changes by preserving lean mass while achieving significant fat loss in humans with obesity.

Key findings

01Weight loss medications can lead to a loss of about 10% of lean mass, similar to aging effects.
02Resistance exercise can significantly increase lean mass and strength in individuals undergoing weight loss treatment.
03Combining resistance training with incretin therapy may help maintain muscle mass and improve overall body composition.

PubMed

#08

The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation.

ReviewInfluence4.0

125

The review highlighted that novel pharmacotherapies, including incretin receptor agonists, can achieve significant weight loss while preserving lean mass during obesity treatment.

PubMed

#09

Emerging pharmacotherapies for obesity: A systematic review.

Kokkorakis Michail, et al. · Pharmacological reviews · 2025

ReviewInfluence4.0

100

The systematic review identified that emerging pharmacotherapies, including retatrutide, show promise for significant weight loss in humans with obesity.

Key findings

01Researchers identified 53 clinical trials for 36 emerging antiobesity drugs, with oral semaglutide being the only one to complete phase 3 trials.
02The study highlighted that completed phase 2 trials showed weight loss ranging from 7.4% to 24.2% with incretin-based therapies.
03There is a need for further research on long-term safety, effectiveness, and the impact of these drugs on obesity-related health issues.

PubMed

#10

Advancements in pharmacological treatment of NAFLD/MASLD: a focus on metabolic and liver-targeted interventions.

ReviewInfluence2.0

Researchers observed that repurposing drugs like retatrutide for NAFLD/MASLD shows promise, although further exploration of their effects on liver histology is needed.

PubMed

Safety

Safety & Handling

Research Gaps

The long-term safety and efficacy of retatrutide in diverse patient populations remain unclear, as ongoing Phase III trials are yet to be completed. Additionally, the specific mechanisms by which retatrutide influences muscle mass retention during weight loss and its potential effects on bone density and fracture risk have not been thoroughly investigated in human subjects.

Solubility

Retatrutide is soluble in water and exhibits moderate solubility in DMSO.

Storage & Handling

Lyophilized

Stable for 2+ years at -20°C, 12 months at 4°C

Reconstituted

Use within 14 days when refrigerated at 4°C

Avoid

Avoid repeated freeze-thaw cycles, direct light

Solvent

Bacteriostatic water or sterile saline recommended

Safety information is derived from published research and may not reflect all known risks. This is not medical advice.

Legal Status

🇩🇪DE

Not approved as a medicinal product. Not a controlled substance. Sale as research chemical is a legal grey area.

🇺🇸US

Not approved by the FDA. Not scheduled by the DEA.

🇦🇺AU

Not approved by the TGA.

🇬🇧UK

Not approved by the MHRA.

Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.

Community Insights

Publications per Year

49 total

Pricing

Price Comparison

BESTResearch Peptides UKUK
40mg
$215.90
Price/mg
$5.40/mg
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Strate LabsUS
20mg
$199.99
Price/mg
$10.00/mg
View
Strate LabsUS
10mg
$129.99
Price/mg
$13.00/mg
View
Prime PeptidesUS
10mg
$140.00
Price/mg
$14.00/mg
View
Strate LabsUS
60mg
$2499.00
Price/mg
$41.65/mg
View

Vendor	Amount	Price	Price/mg	Link
BESTResearch Peptides UKUK	40mg	$215.90	$5.40/mg	View
Strate LabsUS	20mg	$199.99	$10.00/mg	View
Strate LabsUS	10mg	$129.99	$13.00/mg	View
Prime PeptidesUS	10mg	$140.00	$14.00/mg	View
Strate LabsUS	60mg	$2499.00	$41.65/mg	View

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Mechanism

Tools

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Mechanism

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Legal Disclaimer

This page is for informational and research purposes only. All information is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Many substances listed may not be approved for human use and may be subject to drug regulation laws (e.g., AMG in Germany, FDA in the US). PepStack does not encourage the use of any substance on humans. Always consult a qualified healthcare professional before making any health-related decisions. Use of this information is entirely at your own risk. PepStack assumes no liability for the accuracy, completeness, or timeliness of the content provided. Full disclaimer