Peptide · Research Monograph · Triple GLP-1/GIP/glucagon receptor agonist peptide (LY3437943)

RT3

A triple-hormone agonist studied for weight loss and metabolic health

RT3 is a next-generation triple hormone agonist - hitting the GLP-1, GIP, and glucagon receptors at once - researched as one of the most powerful compounds yet studied for weight loss and metabolic health.

For laboratory research use only - not for human or animal use

In the On Top Labs catalog - RT3 from $99.99 Certificate of analysis (PDF)

Molecular data

Molecular formulaC221H342N50O68
Molecular weight4731.32 Da
SequenceRT3 (LY3437943) - synthetic triagonist peptide; full sequence not disclosed on page
Sequence length39 residues
CAS / identifierLY3437943 (CAS 2381089-83-2)
Physical formLyophilized powder
Available sizes10mg, 15mg, 24mg, 30mg, 48mg, 60mg

How it works

GLP-1R

GLP-1 Receptor Agonism

Activates GLP-1 receptors to enhance glucose-dependent insulin secretion, suppress glucagon release, delay gastric emptying, and engage central appetite regulation pathways in the hypothalamus. This is the same pathway targeted by semaglutide and liraglutide.

  • Glucose-dependent insulin secretion
  • Delayed gastric emptying
  • Central appetite suppression
GIPR

GIP Receptor Agonism

Co-agonism at GIP receptors potentiates the metabolic effects of GLP-1 signaling, enhances lipid metabolism, and modulates adipose tissue remodeling. This dual GLP-1/GIP mechanism is shared with tirzepatide, but RT3 adds a third target.

  • Synergistic insulin potentiation
  • Lipid metabolism enhancement
  • Adipose tissue signaling
GCGR

Glucagon Receptor Agonism

The unique third target - glucagon receptor activation increases hepatic energy expenditure, promotes fatty acid oxidation, and drives thermogenesis. This differentiates RT3 from all dual agonists and may account for its superior weight reduction in trials.

  • Hepatic energy expenditure increase
  • Enhanced fatty acid oxidation
  • Thermogenic pathway activation

What the research shows

Metabolic

Obesity & Weight Management

RT3 demonstrated up to 24.2% body weight reduction at 48 weeks in the Phase 2 obesity trial - the largest reduction reported for any anti-obesity compound in a randomized trial at that time.

Jastreboff et al. 2023

Endocrine

Type 2 Diabetes

In subjects with T2DM, RT3 reduced HbA1c by up to 2.16% and fasting glucose by up to 69.1 mg/dL, with weight loss up to 16.94% - exceeding most dual-agonist results in comparable populations.

Panou et al. 2026

Hepatic

Liver Fat Reduction (MASLD/MASH)

RT3 has shown marked reductions in liver fat content in preclinical and early clinical data, positioning it as a candidate for metabolic dysfunction-associated steatotic liver disease research.

Malandris et al. 2026

Comparative

Triple vs Dual Agonism

Network meta-analysis shows RT3 achieved the largest weight loss and HbA1c reduction among all glucagon receptor agonists studied, surpassing survodutide, mazdutide, and cotadutide.

Abulehia et al. 2026

Specification

Compound ClassTriple GLP-1/GIP/Glucagon receptor agonist
Research NameLY3437943 (RT3)
TargetsGLP-1R + GIPR + GCGR
FormLyophilized powder
Purity≥99% (HPLC verified)
TestingThird-party HPLC, Mass Spec, Endotoxin
Storage (lyophilized)-20°C for long-term stability
Storage (reconstituted)2-8°C, use within 14 days
SolubilityBacteriostatic water for reconstitution
COAIncluded with every order
Stability24 months from manufacture date when stored properly
AppearanceWhite to off-white powder
Molecular FormulaAvailable on request

Frequently asked questions

What is RT3?

RT3 (LY3437943) is a first-in-class triple hormone receptor agonist. It simultaneously targets three receptors: GLP-1 (appetite and insulin), GIP (metabolic potentiation), and glucagon (energy expenditure). This triple mechanism distinguishes it from single-agonists like semaglutide and dual-agonists like tirzepatide.

How does RT3 differ from semaglutide and tirzepatide?

Semaglutide (Ozempic/Wegovy) targets GLP-1 only. Tirzepatide (Mounjaro/Zepbound) targets GLP-1 + GIP (dual agonist). RT3 targets GLP-1 + GIP + Glucagon (triple agonist). In the Phase 2 trial, RT3 achieved 24.2% body weight reduction at 48 weeks - higher than any published result for semaglutide (~15%) or tirzepatide (~22%) at comparable timepoints.

What were the key Phase 2 trial results?

In the Jastreboff et al. 2023 NEJM trial (n=338, 48 weeks): the 12mg dose produced 24.2% mean body weight reduction. 92% of participants lost ≥5% body weight, 75% lost ≥10%, and 60% lost ≥15%. The effect was dose-dependent, with even the 1mg dose achieving 8.7% reduction.

Is RT3 FDA approved?

No. RT3 is currently in Phase 3 clinical trials (the TRIUMPH program). RT3 is a research compound sold exclusively for in vitro laboratory research. It is not FDA approved and should not be confused with approved medications.

How should RT3 be stored?

Store lyophilized at -20°C for long-term stability. After reconstitution with bacteriostatic water, refrigerate at 2-8°C and use within 14 days. Protect from direct light and avoid repeated freeze-thaw cycles.

Literature

  • NEJM Triple-Hormone-Receptor Agonist RT3 for Obesity - A Phase 2 Trial 2023 · Jastreboff AM et al. · PMID: 37366315
  • Review RT3 in type 2 diabetes mellitus and obesity: an overview 2026 · Panou T et al.
  • Meta-Analysis Comparative Efficacy and Safety of Glucagon Receptor Agonists: A Network Meta-Analysis 2026 · Abulehia A et al.
  • Preclinical RT3 Shows Multiple Metabolic Benefits in Diet-Induced Obese MASH Mouse and Hamster Models 2026 · Briand F et al.

For laboratory research use only. Not a drug, supplement, or medical product; not for human or animal use. All findings referenced are from published preclinical/laboratory research.