A triple-receptor peptide that engages GLP-1, GIP, and glucagon pathways at once — the three core signals studied in glucose handling, appetite regulation, and lipid metabolism. The most advanced triple-incretin analog in peer-reviewed research.
Jastreboff et al. — 48-wk Phase 2 RCT. All data from peer-reviewed literature. For Research Use Only — Not for Human Consumption.
Preclinical Data
Data from peer-reviewed publications and Phase 2 trial registrations. Cited from independent published literature. For Research Use Only.
24%
Mean body weight change observed, 48 wks, 12 mg/wk vs placebo in Phase 2 RCT.
Jastreboff et al., NEJM 2023
3×
Receptor pathways engaged simultaneously in vitro.
Phase 2 Mechanism Data
48wk
Phase 2 duration. No dose-response plateau in the highest-dose cohort at endpoint.
Eli Lilly Phase 2 Trial
2,500+
Participants enrolled across active Phase 3 TRIUMPH trials. Est. completion 2026–27.
ClinicalTrials.gov
Dose-Response: Body Weight Change
Phase 2 RCT · % change from baseline at 48 weeks by weekly dose
Phase 2 RCT · N=338 · Jastreboff et al., NEJM 2023 [1]. In vitro research use only.
Mechanism of Action
GLP-3 RT engages all three receptors simultaneously in vitro. Each triggers a distinct, complementary pathway in preclinical models.
GLP-1 Receptor
Insulin secretion · Appetite signaling · Gastric emptying
0.04 nM
GIP Receptor
Adipocyte lipid metabolism · Insulin sensitization
0.06 nM
Glucagon Receptor
Hepatic glucose regulation · Thermogenesis · NASH
0.28 nM
Why the glucagon receptor changes everything
GCGR co-agonism engages hepatic and thermogenic pathways not activated by GLP-1R or GIPR alone. Preclinical NASH models have examined GCGR-associated hepatic fat changes and UCP-1 expression in brown adipose tissue (Sloop et al., Cell Metabolism 2022). In vitro and preclinical observations only.
Triple-agonist signaling map
One 39-residue backbone engages all three receptors, then branches into three complementary metabolic axes.
Receptor EC50 from in vitro cAMP assays (Coskun et al., J Med Chem 2022). GCGR-associated hepatic & thermogenic pathways per Sloop et al., Cell Metabolism 2022. Illustrative schematic — in vitro / preclinical observations, research use only.
Compound Comparison
Three generations of research compounds at their highest studied doses.
Scroll to see full table →
| Compound | GLP-1R | GIPR | GCGR | t½ | Phase | ΔBW |
|---|---|---|---|---|---|---|
| GLP-3 RTTriple | ✓ | ✓ | ✓ | ~6d | Ph.3 | −24.2% |
| GLP-2 TZDual | ✓ | ✓ | — | ~5d | Appr. | −20.9% |
| GLP-1 SSingle | ✓ | — | — | ~7d | Appr. | −14.9% |
| GLPSingle | ✓ | — | — | 13hr | Appr. | −8.0% |
ΔBW = mean % change from baseline at the highest-dose cohort in published peer-reviewed trials. Trial designs, populations and durations differ significantly. Not a comparative-effectiveness claim. For Research Use Only.
Receptor Selectivity Profile
GLP-3 RT's balanced triple-receptor engagement vs tirzepatide (dual) and semaglutide (mono). EC50 from in vitro cAMP assays — Coskun et al. J Med Chem 2022.
Pharmacokinetic Profile
GLP-3 RT uses the same C18 fatty diacid albumin-binding strategy as semaglutide, with a ~144-hour modeled plasma half-life. Curve draws on scroll.
Compound Profile
Molecular and pharmacological specs from published preclinical literature and Eon Peptides batch records.
| Common Name | GLP-3 RT |
| Code | LY3437943 |
| Class | GLP-1 / GIP / Glucagon Triple Agonist |
| Structure | 39-amino acid acylated peptide |
| Mol. Weight | ~4.7 kDa |
| Half-Life | ~6 days (weekly dosing) |
| Acylation | C18 fatty diacid · albumin binding |
| Developer | Eli Lilly and Company |
| Phase | Phase 3 · TRIUMPH |
| Purity | ≥99% HPLC Verified |
| Form | Lyophilized powder · sealed vial |
| Regulatory | Research Use Only — Not for Human Use |
Receptor Binding Affinity
EC50 from in vitro cAMP assays. Lower = stronger binding.
Sub-nanomolar binding at all three receptors. GLP-1R and GIPR both below 0.1 nM — the balanced agonism profile cited across Phase 2 summaries. In vitro only [2].
Why the C18 acyl chain matters
The C18 fatty diacid modification enables albumin binding, extending half-life to ~6 days. Same strategy as semaglutide — making once-weekly research dosing viable.
Research Context
GLP-3 RT has progressed from Phase 1 first-in-human to Phase 3 enrollment. Timeline from published literature and ClinicalTrials.gov.
Active preclinical & Phase 3 stage
Literature spans NASH/MASH, cardiovascular, and receptor pharmacology.
TRIUMPH Phase 3 initiated
Multiple parallel trials — metabolic, cardiovascular, hepatic (MASH), renal. Completion est. 2026–27.
Phase 2 results published
Mean BW change of −24.2% at 48 weeks, no dose-response plateau at endpoint. Jastreboff et al. [1].
First-in-human PK/PD study
Confirms ~6-day half-life. Weekly subcutaneous protocol established [6].
Initial synthesis & characterization
LY3437943 identified as balanced triple agonist. Sub-nM binding confirmed at all three receptors.
Key preclinical observations
No dose-response plateau observed at 48 weeks in any dose cohort.
Jastreboff et al., NEJM 2023 [1]
GIPR co-agonism appears associated with attenuated GI adverse events in Phase 2 tolerability analysis.
Jastreboff et al., NEJM 2023 [1]
GCGR activation associated with hepatic fat reduction independent of caloric restriction in NASH models.
MASH Preclinical Models, 2023
Insulin sensitivity improvements observed independent of weight reduction.
Phase 2 Metabolic Substudy [1]
Storage & Handling
Proper handling is the difference between a viable sample and a degraded one.
Pre-Reconstitution
−20°C
Sealed in freezer. Stable 24 months. Avoid frost-free — temp cycling degrades structure.
Post-Reconstitution
2–8°C
Transfer to 2–8°C immediately. Do not freeze reconstituted material.
Reconstitution
BAC Water
2 mL BAC water per vial via calibrated laboratory syringe. Direct along interior vial wall slowly.
Critical Avoids
Avoid
No shaking or vortex. No UV light. Discard if cloudy or particulate after reconstitution.
Laboratory Reconstitution Reference
Standard laboratory procedure for qualified researchers. In vitro research use only.
Equilibrate to room temp
Remove from −20°C. Allow 15–20 min passive equilibration. Do not apply heat.
Add bacteriostatic water
Draw 2 mL BAC water. Direct solvent slowly along the interior glass wall — not onto the lyophilized cake.
Dissolve by rotation
Roll between palms 30–60 seconds until clear. Never shake or vortex.
Inspect and label
Should be clear, colorless to faint yellow. Discard if cloudy. Label with compound, concentration, date.
Label and refrigerate
Transfer immediately to 2–8°C. Label with lot number and reconstitution date. Do not freeze.
Published Literature
Independent peer-reviewed studies. Not Eon Peptides claims.
Triple-Hormone-Receptor Agonist GLP-3 RT (LY3437943) — Phase 2 Dose-Finding, 48-Week RCT
Phase 2 RCT evaluating once-weekly subcutaneous GLP-3 RT in adults with obesity. At 48 weeks, the 12 mg cohort showed −24.2% mean body weight change from baseline, with no plateau at endpoint. N=338 across 5 dose cohorts.
Design and Characterization of LY3437943, a Novel Triple GIP, GLP-1, and Glucagon Receptor Agonist
Characterization of LY3437943 as a balanced acylated peptide agonist. In vitro cAMP assays confirmed sub-nanomolar EC50 at all three receptors: GLP-1R 0.04 nM, GIPR 0.06 nM, GCGR 0.28 nM.
Glucagon Receptor Agonism in Triple Agonist Therapy: Hepatic Fat Reduction in MASH Models
Preclinical GCGR co-agonism study in MASH models. Reduction in hepatic triglyceride content and liver enzymes independent of caloric restriction.
Cardiovascular Outcomes in GLP-1/GIP/Glucagon Triple Agonism
Preclinical CV safety and efficacy of triple receptor agonism. Reductions in systolic blood pressure, fasting glucose, and triglycerides.
GIPR Co-Agonism Attenuates GLP-1R-Mediated Nausea
GI tolerability analysis from the Phase 2 trial. GIPR co-agonism appears to attenuate GLP-1R-mediated nausea.
Next-Generation Incretin Therapeutics: Systematic Review of Triple Receptor Agonism
Systematic review of 40+ studies on triple agonist pharmacology. Authors conclude GCGR co-agonism provides additive hepatic and thermogenic effects.
TRIUMPH-1: Phase 3 Trial of GLP-3 RT in Adults with Obesity (NCT05536804)
Pivotal Phase 3 trial of once-weekly GLP-3 RT vs placebo, 2,500+ adults with BMI ≥30. Primary endpoint: % body weight change at 72 weeks.
TRIUMPH-NASH: Phase 3 Evaluation of GLP-3 RT in MASH
Phase 3 trial in MASH with liver fibrosis. Primary endpoints: histological MASH resolution and ≥1 stage fibrosis improvement.
Thermogenic Contribution of Glucagon Receptor Agonism: BAT Activation in DIO Models
GCGR agonism demonstrated brown adipose tissue activation (UCP-1 expression, oxygen consumption) in DIO models.
Indexed from PubMed, ClinicalTrials.gov, and peer-reviewed journals. Independent published research — not Eon Peptides claims. For Research Use Only — Not for Human Consumption.
Cited Sources
All scientific claims sourced from peer-reviewed literature or official trial registrations.
Triple-Hormone-Receptor Agonist GLP-3 RT for Obesity — A Phase 2 Trial
LY3437943, a Novel Triple GIP, GLP-1, and Glucagon Receptor Agonist
Glucagon Receptor Agonism and Hepatic Fat Reduction in MASH Preclinical Models
Thermogenic Contribution of Glucagon Receptor Agonism: BAT Activation in DIO Models
Pharmacokinetics of LY3437943 Enabled by C18 Fatty Diacid Acylation
First-in-Human Phase 1 Study of LY3437943
TRIUMPH-1: A Phase 3 Study of GLP-3 RT in Participants with Obesity
Next-Generation Incretin Therapeutics: Systematic Review of Triple Receptor Agonism