Wiki · Profile

Retatrutide

LY3437943

Metabolic & WeightPhase III

MW: 4731g/mol
Formula: C221H342N46O68

Retatrutide is a novel synthetic peptide classified as a triple agonist, activating the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors. Researchers primarily study retatrutide for its potential efficacy in managing obesity and related metabolic conditions, as well as its effects on glycemic control in individuals with type 2 diabetes. Key findings from recent studies indicate that retatrutide can lead to significant reductions in body weight, with participants experiencing weight loss of up to 24.2% after 48 weeks of treatment, alongside meaningful improvements in glycemic parameters. Current research is focused on ongoing clinical trials assessing its safety and efficacy across various populations, including those with obesity, obstructive sleep apnea, and knee osteoarthritis.

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 activates the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors, leading to enhanced insulin secretion, reduced glucagon release, and increased energy expenditure. This activation engages multiple signaling pathways, including the cAMP/PKA pathway for GLP-1 and GIP receptors, and the cAMP/PKA and ERK1/2 pathways for glucagon receptors, promoting satiety, weight loss, and improved glycemic control. While the overall mechanism is well-characterized, the precise interactions and contributions of each receptor in various biological processes remain an area of ongoing research.

Research

65 Research Publications

3,070

Total Citations

Human/RCT

6.4

Avg. Influence

2026

Latest

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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

HumanInfluence87.0

645

The study demonstrated that retatrutide administration in adults with obesity resulted in significant weight reductions of up to 24.2% after 48 weeks, with gastrointestinal adverse events being the most common.

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 weeks0.5 mgsubcutaneous(human)24 weeks4 mgsubcutaneous(human)24 weeks8 mgsubcutaneous(human)24 weeks12 mgsubcutaneous(human)24 weeks4 mgsubcutaneous(human)40 weeks9 mgsubcutaneous(human)40 weeks12 mgsubcutaneous(human)40 weeks

PubMed

02Top

#02

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

Drucker Daniel J · Diabetes care · 2024

ReviewInfluence9.0

276

Researchers observed that the rapid development of GLP-1-based medicines, including retatrutide, offers promising efficacy for various metabolic disorders, while highlighting safety concerns related to muscle strength and gastrointestinal health.

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

What is the pipeline for future medications for obesity?

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

ReviewInfluence7.0

275

Researchers observed that retatrutide, along with other combination therapies, is positioned to enhance weight loss efficacy in obesity treatment, potentially rivaling results seen with bariatric surgery.

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

#04

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

HumanInfluence36.0

274

The study demonstrated that retatrutide significantly improved glycemic control and reduced body weight in people with type 2 diabetes, with a safety profile consistent with other GLP-1 receptor agonists.

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

#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

HumanInfluence15.0

226

The study demonstrated that retatrutide significantly reduced liver fat in participants with metabolic dysfunction-associated steatotic liver disease, achieving normal liver fat levels in a substantial proportion of subjects.

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

ReviewInfluence3.0

123

Researchers observed that combining resistance exercise with incretin-based therapies like retatrutide may help preserve lean mass during significant weight loss, addressing concerns about muscle loss.

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

106

Researchers observed that while weight loss from pharmacotherapy can lead to loss of fat-free mass, novel compounds may preserve lean mass during significant weight reduction.

PubMed

#09

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

ReviewInfluence2.0

The study demonstrated that combination therapies for NAFLD/MASLD, including repurposed drugs like retatrutide, may improve treatment outcomes, particularly in patients with advanced disease.

PubMed

#10

Emerging pharmacotherapies for obesity: A systematic review.

Kokkorakis Michail, et al. · Pharmacological reviews · 2025

ReviewInfluence2.0

The systematic review identified that emerging pharmacotherapies, particularly incretin analogs like retatrutide, show promising efficacy for weight loss in adults with obesity, while emphasizing the need for long-term safety data.

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

Safety

Safety & Handling

Research Gaps

The dose-response relationships of retatrutide concerning side effects, safety, and efficacy for obesity treatment are not yet fully understood, particularly regarding long-term effects and potential risks associated with prolonged use. Additionally, the specific mechanisms underlying the simultaneous activation of the glucose-dependent insulinotropic polypeptide, GLP-1, and glucagon receptors by retatrutide remain unclear, necessitating further investigation into its pharmacodynamics and interactions.

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

48 total

Pricing

Price Comparison

BESTStrate LabsUS
20mg
$199.99
Price/mg
$10.00/mg
View
Research Peptides EuropeEU
30mg
$345.59
Price/mg
$11.52/mg
View
Research Peptides EuropeEU
20mg
$248.39
Price/mg
$12.42/mg
View
Strate LabsUS
10mg
$129.99
Price/mg
$13.00/mg
View
Research Peptides EuropeEU
10mg
$134.99
Price/mg
$13.50/mg
View

Vendor	Amount	Price	Price/mg	Link
BESTStrate LabsUS	20mg	$199.99	$10.00/mg	View
Research Peptides EuropeEU	30mg	$345.59	$11.52/mg	View
Research Peptides EuropeEU	20mg	$248.39	$12.42/mg	View
Strate LabsUS	10mg	$129.99	$13.00/mg	View
Research Peptides EuropeEU	10mg	$134.99	$13.50/mg	View

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Mechanism

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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