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GLP-3 (R)
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GLP-3 (R)

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GLP-3 (Glucagon-Like Peptide-3) is a lesser-known member of the glucagon peptide family studied for its role in gastrointestinal growth and repair pathways. Research focuses include mucosal regeneration, cellular proliferation in intestinal models, and peptide receptor interaction studies.

Weight .06 kg
Size

5 mg, 10 mg, 15 mg, 30 mg, 60 mg
Shelf Life

36 months
Storage

Lyophilized: freeze at ?20 °C (?4 °F)
Reconstituted: refrigerate at 2–8 °C (35.6–46.4 °F) and use within 3–6 months.
Molecular Formula

C???H???N??O??
PubChem CID

485663353
http://www.pubchem.ncbi.nlm.nih.gov/substance/485663353
Disclaimer

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. For research purposes only. Not for human consumption.

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Research Compound Profile

GLP-3

Also known as:Reta******* · Triple Agonist Category:Metabolic Clinical Status:Phase 3 Active (TRIUMPH Program) FDA Status:Not Approved · Investigational

A first-in-class triple-receptor agonist targeting GIP, GLP-1, and glucagon receptors simultaneously. GLP-3 has demonstrated unprecedented results in clinical trials, with up to 28.7% body weight reduction in Phase 3 studies.

Explore the Research ↓
🧬Peptide Type

Triple-Receptor Agonist (GIP/GLP-1/Glucagon)

📊Receptor Targets

3 — GIP, GLP-1, and Glucagon receptors

🔬Primary Research Focus

Obesity, weight management & metabolic disease

🧪Development Stage

Phase 3 Active (TRIUMPH Program)

What Is GLP-3?

🧠 Simple Explanation

GLP-3 (Reta*******) is a new type. Think of it as three drugs in one molecule — it activates three different hormone receptors in your body that control appetite, blood sugar, and energy burning. In clinical trials, it has produced the highest weight loss results ever seen in an obesity medication.

Unlike GLP-1 (which targets one receptor) or GLP-2 (which targets two), GLP-3 simultaneously activates GIP, GLP-1, and glucagon receptors — earning it the designation of "triple agonist."

🔬 Advanced Context

GLP-3 (Reta*******) is a synthetic peptide engineered to simultaneously agonize three incretin-related receptors: the glucagon-like peptide-1 receptor (GLP-1R), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon receptor (GCGR). It inhibits human GCGR, GIPR, and GLP-1R with EC50 values of 5.79, 0.0643, and 0.775 nM respectively.

The compound has a half-life of approximately 6 days, enabling once-weekly subcutaneous administration. In the Phase 2 trial (NCT04881760), the 12mg weekly dose produced 24.2% mean body weight loss at 48 weeks. The Phase 3 TRIUMPH-4 trial subsequently demonstrated 28.7% body weight loss at the 12mg dose over 68 weeks — the highest ever recorded in a Phase 3 obesity trial.

The triple-agonist design addresses limitations of single- and dual-receptor approaches. GLP-1 activation reduces appetite and slows gastric emptying. GIP activation improves insulin sensitivity and fat distribution. The glucagon component uniquely increases energy expenditure via thermogenesis and promotes lipolysis. FDA submission is estimated for Q4 2026 or Q1 2027.

How It Works

Triple-receptor mechanism of action based on clinical evidence

STEP 01→

GLP-1 Receptor Activation

GLP-3 activates GLP-1 receptors in the hypothalamus, pancreatic beta cells, and gastrointestinal tract. This reduces appetite signaling, stimulates glucose-dependent insulin secretion, and delays gastric emptying.

💡 Simple Translation

The medication activates a receptor in your brain's appetite center that makes you feel less hungry. It also slows how fast food leaves your stomach, so you feel full longer after eating.

STEP 02→

GIP Receptor Activation

Simultaneous GIP receptor agonism enhances insulin sensitivity in adipose tissue and pancreatic cells. GIPR activation promotes favorable fat redistribution, reducing visceral adiposity while improving glucose uptake.

💡 Simple Translation

A second receptor target helps your body respond better to insulin and shifts where fat is stored — away from around your organs toward less harmful locations under the skin.

STEP 03→

Glucagon Receptor Activation

The glucagon receptor component increases hepatic fat oxidation and activates brown adipose tissue thermogenesis. This elevates resting energy expenditure and promotes lipolysis — the breakdown of stored triglycerides into free fatty acids.

💡 Simple Translation

A third receptor — unique to GLP-3 — tells your body to burn more calories at rest by generating heat and breaking down stored fat for energy, like turning up your internal thermostat.

STEP 04

Combined Clinical Outcome

The synergistic triple-agonist effect produced 24.2% mean body weight loss at 48 weeks (Phase 2) and 28.7% at 68 weeks (Phase 3 TRIUMPH-4). HbA1c decreased by 0.4% on average. Glucagon's glucose-raising effects were offset by GLP-1/GIP insulin stimulation.

💡 Simple Translation

Together, the three pathways produce more weight loss than any single or dual approach — participants lost nearly 29% of their body weight in the largest trial, while blood sugar also improved.

Clinical Development Status

Current position in the regulatory pipeline

✓
Preclinical

Laboratory and animal studies. Triple-agonist receptor characterization published in Cell Metabolism (2022).

✓
Phase 1

First-in-human safety and pharmacokinetics completed. Once-weekly dosing established.

✓
Phase 2

NCT04881760: 24.2% weight loss at 48 weeks with 12mg dose. Published in NEJM August 2023.

4
Phase 3

TRIUMPH program active. TRIUMPH-4 topline results: 28.7% weight loss at 68 weeks (Dec 2025).

5
Phase 4

Post-approval surveillance studies to follow. Not yet initiated.

6
FDA Approved

FDA submission estimated Q4 2026–Q1 2027. Potential approval in 2027–2028.

Phase 2 completed (NCT04881760). Phase 3 TRIUMPH program active. FDA submission estimated Q4 2026–Q1 2027. Not approved for any indication.

What Does the Research Show?

Summary of clinical findings from published trials

📊Key Findings
  • 28.7% mean body weight loss at 68 weeks in Phase 3 (TRIUMPH-4)
  • 24.2% body weight loss at 48 weeks in Phase 2 trial (12mg dose)
  • HbA1c reduced by 0.4% on average despite glucagon activity
  • Approximately ~6-day half-life
📈Research Milestones
  • Developed as first-in-class triple agonist
  • Phase 2 trial (NCT04881760) published in NEJM, August 2023
  • Phase 3 TRIUMPH program launched with multiple trials
  • TRIUMPH-4 topline results reported December 2025
🔬Mechanism Highlights
  • Simultaneous activation of GIP, GLP-1, and glucagon receptors
  • GLP-1: appetite suppression and delayed gastric emptying
  • GIP: improved insulin sensitivity and favorable fat redistribution
  • Glucagon: increased thermogenesis, lipolysis, and resting energy expenditure
🧪Safety Profile in Trials
  • Most common side effects: GI-related (nausea, diarrhea, vomiting)
  • GI events mostly mild-to-moderate, decreasing over time
  • Dose-escalation protocol reduces initial GI side effects
  • New safety signal in Phase 3: abnormal sense of touch (paresthesia) reported

Published Findings

Clinical trials and peer-reviewed studies with linked sources

StudyModelKey FindingYearSource
Phase 2 dose-finding trialHuman (n=338)24.2% mean body weight loss at 48 weeks with 12mg weekly dose; dose-dependent efficacy across all dose levels2023NEJM ↗
TRIUMPH-4 Phase 3 trialHuman (Phase 3)28.7% mean body weight loss at 68 weeks with 12mg dose — highest weight loss in any Phase 3 obesity trial2025Eli Lilly ↗
Triple agonist mechanism characterizationIn Vitro / AnimalEC50 values: GCGR 5.79 nM, GIPR 0.0643 nM, GLP-1R 0.775 nM; simultaneous activation of all three receptors2022Cell Metabolism ↗
Type 2 diabetes efficacyHuman (n=281)HbA1c reductions of up to 2.02% at 36 weeks; significant improvements in glycemic control2023The Lancet ↗
Metabolic effects & liver fatHuman (Phase 2 substudy)Significant reductions in liver fat content; improvements in metabolic syndrome markers2024ClinicalTrials.gov ↗
Comparison vs GLP-2 and GLP-1Cross-trial AnalysisGLP-3 (24.2%) outperformed GLP-2 (~22%) and GLP-1 (~15-17%) at maximum doses in comparable trial durations2024Multiple Sources ↗

⚠️ GLP-3 is in active Phase 3 clinical trials. Cross-trial comparisons should be interpreted cautiously due to differences in study design, populations, and endpoints.

Research Timeline

Key milestones in GLP-3 investigation

2018

Discovery & Development

Development begins as a novel triple-agonist peptide targeting GIP, GLP-1, and glucagon receptors

2021

Phase 1 Completed

First-in-human safety and pharmacokinetics trials completed

2022

Phase 2 Trial Initiated

Dose-finding study (NCT04881760) enrolls 338 participants with obesity

2023

Phase 2 Results Published

NEJM publishes landmark results: 24.2% weight loss at 48 weeks — highest ever for an obesity drug at the time

2023

Type 2 Diabetes Data

The Lancet publishes Phase 2 diabetes trial results showing HbA1c reductions of up to 2.02% at 36 weeks

2024

TRIUMPH Program Launches

Initiation of Phase 3 TRIUMPH clinical trial program with multiple studies across different populations

2025

Phase 3 Results (TRIUMPH-4)

Topline results show 28.7% mean weight loss at 68 weeks — new record for Phase 3 obesity trials

2027

Expected FDA Decision

FDA submission estimated Q4 2026–Q1 2027; potential approval for obesity and overweight indications

Molecular Profile

Physicochemical characteristics and pharmacokinetic parameters

Molecular Formula

C₂₂₁H₃₄₂N₄₆O₆₈

Structure Type

Synthetic Peptide (Triple Agonist)

CAS Number

2381089-83-2

PubChem CID

171390338

Developer Code

LY3437943

Half-Life

~6 days

Administration

Subcutaneous studied

Storage

Refrigerated 2–8°C

Reference: PubChem CID 171390338

Research Applications

Areas of active clinical investigation

Investigated for chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with comorbidities

Studied in Type 2 diabetes for glycemic control alongside weight reduction

Explored for metabolic-associated steatotic liver disease (MASLD/NAFLD) with significant liver fat reductions

Examined for cardiovascular risk reduction through weight loss and metabolic improvements

Evaluated for obstructive sleep apnea improvements secondary to weight reduction

Assessed for potential in metabolic syndrome — addressing insulin resistance, dyslipidemia, and hypertension

Investigated for long-term weight maintenance and prevention of weight regain

Studied in comparison protocols alongside GLP-1 and GLP-2 for efficacy benchmarking

Why It Arrives as a Powder

Understanding lyophilized formulation in research peptides

❄️

Stability Preservation

Lyophilization (freeze-drying) removes water content, significantly reducing the rate of chemical degradation that occurs in liquid solutions. This preserves the peptide's structural integrity during storage and transport.

📅

Extended Shelf Life

Dry powder form can maintain potency at -20°C for extended periods, far exceeding the approximately 30-day window available for reconstituted liquid preparations.

🛡️

Degradation Prevention

Peptide bonds are susceptible to hydrolysis in aqueous environments. Removing the solvent eliminates this primary degradation pathway, reducing the risk of fragmentation and loss of biological activity.

🔬

Laboratory Preparation Standards

Reconstitution in research settings follows established protocols using bacteriostatic water or sterile saline, allowing precise concentration control appropriate for the specific experimental design.

✅

Sterile Research Conditions

Lyophilized preparations are typically processed under controlled, low-bioburden environments. Proper aseptic technique during reconstitution maintains the sterility required for reliable research outcomes.

Transparency & Quality Verification

Analytical standards applied to research-grade peptide materials

🧪

Third-Party Analytical Testing

Independent laboratories perform comprehensive analysis on each production batch, ensuring unbiased verification of compound identity and purity.

📊

Purity Verification (HPLC)

High-Performance Liquid Chromatography confirms peptide purity levels, typically targeting ≥98% for research-grade material.

🔬

Identity Confirmation (Mass Spectrometry)

Mass spectrometry validates molecular weight and structural identity, confirming the compound matches its expected profile.

📋

Batch-Specific Certificates of Analysis

Each lot is accompanied by a unique COA detailing purity percentage, lot number, test date, labeled vs. actual content, and testing laboratory.

📁

Documentation Transparency

All analytical results, testing methodologies, and laboratory credentials are made available for researcher review and institutional compliance.

🌡️

Storage Verification Standards

Cold-chain integrity monitoring ensures proper temperature maintenance from production through delivery, preserving compound stability.

Frequently Asked Questions

Common inquiries about GLP-3 research

GLP-3 (Reta*******) is an investigational synthetic peptide. It is the first triple-receptor agonist designed to simultaneously activate three metabolic hormone receptors: GLP-1, GIP, and glucagon. Unlike naturally occurring hormones, it is an engineered molecule.
GLP-3 has completed Phase 1 and Phase 2 clinical trials and is currently in Phase 3, which includes multiple studies across different patient populations. The Phase 2 trial results were published in the New England Journal of Medicine in August 2023. The TRIUMPH-4 Phase 3 trial reported topline results in December 2025 showing 28.7% weight loss. FDA submission is estimated for Q4 2026 or Q1 2027, with potential approval in 2027–2028.
In the Phase 2 trial (n=338), the 12mg weekly dose produced 24.2% mean body weight loss at 48 weeks — approximately 58 pounds for a 240-pound individual. The Phase 3 TRIUMPH-4 trial subsequently showed 28.7% weight loss at 68 weeks, the highest ever recorded in a Phase 3 obesity trial. For comparison, GLP-2 (dual agonist) produces approximately 22% weight loss and GLP-1 (single agonist) approximately 15–17% at maximum doses.
GLP-3 is administered as a once-weekly subcutaneous injection. Clinical trials used a dose-escalation protocol, starting at lower doses (typically 0.5mg) and gradually increasing over 20–24 weeks to the target maintenance dose (up to 12mg). This titration approach helps minimise gastrointestinal side effects. Injection sites include the abdomen, thigh, or upper arm.
The most common side effects are gastrointestinal: nausea, diarrhea, vomiting, and constipation. These were mostly mild-to-moderate and tended to decrease over time. In Phase 3, a new safety signal of abnormal sense of touch (paresthesia) was reported. Because the compound activates glucagon receptors, there were theoretical concerns about blood sugar increases, but the GLP-1 and GIP components effectively counterbalanced this — HbA1c actually decreased by 0.4% on average.
GLP-1 refers to single-agonist medications that target only the GLP-1 receptor (e.g., sema*******). GLP-2 refers to dual-agonist medications that target GLP-1 and GIP receptors (e.g., tirz*******). GLP-3 refers to triple-agonist medications that target GLP-1, GIP, and glucagon receptors (e.g., reta*******). Each additional receptor target has produced incrementally greater weight loss in clinical trials: ~15-17% (GLP-1), ~22% (GLP-2), ~29% (GLP-3).
In Phase 2 trials, significant weight loss was observable within the first 12 weeks, with continued loss through 48 weeks. The dose-escalation period (first 20–24 weeks) meant that peak efficacy was reached once participants achieved their target dose. Weight loss appeared to continue throughout the study period without plateauing at 48 weeks, which is why the 68-week Phase 3 data showed even greater results (28.7% vs 24.2%).
No. GLP-3 (Retatrutide) is not approved by the FDA or any regulatory agency for any indication. It is an investigational drug available only through clinical trials. It is expected to submit for FDA approval in Q4 2026 or Q1 2027, with a potential approval decision in 2027–2028.
Because GLP-3 has not completed the full clinical trial process required for regulatory approval. While Phase 2 and early Phase 3 results are highly promising, the TRIUMPH program includes additional Phase 3 trials that must be completed. The FDA requires comprehensive data on efficacy, safety, and manufacturing quality before granting approval.
The Phase 3 TRIUMPH-4 trial evaluated outcomes at 68 weeks (approximately 16 months). Longer-term studies are part of the TRIUMPH program. Key questions remain about weight maintenance after discontinuation, long-term cardiovascular outcomes, and the durability of metabolic improvements. As with other GLP-1 class medications, weight regain after stopping treatment is a significant area of ongoing investigation.
Clinical trials have primarily studied GLP-3 as monotherapy alongside lifestyle modifications (diet and exercise). Combination studies with other weight management medications have not yet been published. The triple-agonist mechanism was designed to address multiple metabolic pathways simultaneously, potentially reducing the need for combination therapy.
This is a key question. Glucagon does raise blood sugar in isolation — but in the context of GLP-3, the simultaneous GLP-1 and GIP receptor activation strongly stimulates insulin secretion, more than compensating for glucagon's glucose-raising effect. The net result observed in Phase 2 trials was a modest HbA1c reduction of 0.4%, not an increase. The glucagon component primarily contributes its energy-expenditure benefits (thermogenesis, lipolysis) without causing hyperglycemia.

Sources & References

Clinical trials, peer-reviewed publications, and reference materials

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

Jastreboff AM, Kaplan LM, Frías JP, et al. · New England Journal of Medicine (2023) · DOI: 10.1056/NEJMoa2301972

Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes ↗

Rosenstock J, Frías JP, Jastreboff AM, et al. · The Lancet (2023) · DOI: 10.1016/S0140-6736(23)01053-X

LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist for glycemic control and weight loss ↗

Coskun T, Urva S, Roell WC, et al. · Cell Metabolism (2022) · DOI: 10.1016/j.cmet.2022.04.001

TRIUMPH-4 Phase 3 Trial Topline Results ↗

Eli Lilly and Company · Eli Lilly Press Release (2025)

A Study of Retatrutide (LY3437943) in Participants With Obesity (NCT04881760) ↗

ClinicalTrials.gov (2022) · NCT04881760

Retatrutide — Compound Summary (CID 171390338) ↗

PubChem · National Center for Biotechnology Information (2024)

⚠️ Important Notice

GLP-3 (Retatrutide) is an investigational drug and is not FDA-approved. This information is for educational purposes only and is not intended to diagnose, treat, cure, or prevent any disease.

All information presented on this page is derived from peer-reviewed clinical trials and published research. Nothing on this page constitutes medical advice, personal recommendations, or encouragement of any kind. Consult a healthcare professional for medical decisions.

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GLP-3 (R)
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Price range: $74.99 through $299.99
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