Compound Library – Retatrutide
Compound Library
Volume I
Phase 3 — TRIUMPH
Retatrutide Triple-receptor agonist
The first peptide to engage GLP-1, GIP, and glucagon receptors simultaneously — and the most extensively studied compound in current metabolic research literature.
CAS Number
2381089-83-2
Class
Triple Agonist
GLP-1 / GIP / GCGR
Developer
Eli Lilly
LY3437943
First Published
NEJM 2023
Jastreboff et al.
Introduction
A new generation of metabolic peptide.
Retatrutide is a synthetic 39-amino-acid peptide developed by Eli Lilly under the development code LY3437943. It was designed from the ground up as a single molecule capable of simultaneously activating three distinct receptors involved in energy homeostasis — GLP-1, GIP, and glucagon (GCGR) — making it the first true triple-receptor agonist to enter advanced clinical development.
What makes retatrutide pharmacologically distinct from its predecessors is the deliberate inclusion of glucagon receptor activity. Earlier generations — semaglutide (GLP-1 only) and tirzepatide (GLP-1 + GIP) — focused on suppressing appetite and improving insulin signalling. Retatrutide adds a third pathway that drives energy expenditure directly through the liver and brown adipose tissue, fundamentally changing the mechanism profile.
The result, in published Phase 2 data, is the largest body weight reduction ever recorded in a mainstream obesity trial — a finding that has reshaped how the metabolic research community thinks about pharmacological weight management. Retatrutide is now in Phase 3 clinical trials (the TRIUMPH program), with FDA approval anticipated in the 2026–2027 window.
Mechanism
Three receptors, one molecule.
Retatrutide’s pharmacology is defined by simultaneous engagement across three distinct G-protein-coupled receptors. Each contributes a different metabolic effect — and the combination is what produces the compound’s research signal.
I.
GLP-1
GLP-1 Receptor
Shared with Semaglutide · TirzepatideGlucagon-like peptide-1 receptor activation. Suppresses appetite via central nervous system pathways, slows gastric emptying, and improves glucose-dependent insulin secretion. The foundation pathway shared by all modern incretin therapies.
II.
GIP
GIP Receptor
Shared with TirzepatideGlucose-dependent insulinotropic polypeptide receptor. Adds a second incretin pathway with effects on insulin sensitivity, lipid metabolism, and adipose tissue function. The addition that distinguished tirzepatide from semaglutide.
III.
GCGR
Glucagon Receptor
Unique to RetatrutideGlucagon receptor activation. Directly increases energy expenditure via hepatic glucose output and brown adipose tissue thermogenesis. The third pathway that defines retatrutide as a true triple agonist — and drives its distinct metabolic signal.
The Differentiator
The glucagon pathway is what separates retatrutide from everything before it.
While GLP-1 and GIP suppress intake, glucagon receptor agonism increases energy output. The combination produces both sides of the energy equation simultaneously — and is associated with the compound’s striking effect on hepatic fat content, with an 81.4% mean reduction in liver fat reported in the NAFLD sub-study (Sanyal et al., Nature Medicine 2024).
Trial Data
The Phase 2 signal.
24.2%
mean body weight reduction · 12mg dose · 48 weeks
The largest body weight reduction ever recorded in a Phase 2 obesity trial — with 83% of high-dose participants achieving ≥15% reduction and 26% achieving ≥30%.
Source — New England Journal of Medicine, June 2023
Dose-Response — 48-Week Endpoint
Dose Group
Mean Weight Δ
≥5% Loss
≥15% Loss
≥25% Loss
Placebo
−2.1%
27%
2%
0%
1mg
−7.2%
63%
12%
0%
4mg
−12.9%
88%
38%
9%
8mg
−17.3%
93%
63%
24%
12mgHighest dose
−24.2%vs −2.1% placebo
100%
83%
48%
Comparative Pharmacology
Three generations of incretin therapy.
Retatrutide sits at the leading edge of a fifteen-year arc in metabolic peptide research. Each generation added receptor coverage. Each generation produced a stronger weight-loss signal in published trials.
Generation I
Semaglutide
GLP-1 only
Peak Weight Loss
14.9%
STEP 1 trial · 68 weeks
Receptor Coverage
Single — GLP-1
FDA Status
Approved (Wegovy, 2021)
First Published
Wilding et al., NEJM 2021
Generation II
Tirzepatide
GLP-1 + GIP
Peak Weight Loss
22.5%
SURMOUNT-1 trial · 72 weeks
Receptor Coverage
Dual — GLP-1, GIP
FDA Status
Approved (Zepbound, 2023)
First Published
Jastreboff et al., NEJM 2022
Generation III
Retatrutide
GLP-1 + GIP + GCGR
Peak Weight Loss
24.2%
Phase 2 · 48 weeks (highest dose)
Receptor Coverage
Triple — GLP-1, GIP, GCGR
FDA Status
Phase 3 (TRIUMPH program)
First Published
Jastreboff et al., NEJM 2023
Selected Literature
The published research footprint.
Retatrutide entered the published literature in 2022 and has rapidly become one of the most actively studied metabolic peptides in current clinical research. The selected publications below establish the foundational pharmacology and clinical signal cited throughout this entry.
i.
Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
New England Journal of Medicine · 2023; 389(6):514–526 · DOI: 10.1056/NEJMoa2301972
ii.
Triple Hormone Receptor Agonist Retatrutide for Metabolic Dysfunction-Associated Steatotic Liver Disease
Nature Medicine · 2024; 30:2071–2080 · 81.4% mean liver fat reduction at 24 weeks
iii.
A Single-Ascending-Dose Phase 1 Study of LY3437943, a Novel Triple GIP/GLP-1/Glucagon Receptor Agonist
Cell Metabolism · 2022; 34(9):1234–1247 · Foundational PK/PD characterisation
iv.
Retatrutide for the Treatment of Type 2 Diabetes — Phase 2 Trial
The Lancet · 2023; 402(10401):529–544 · Glycaemic and weight-loss endpoints in T2D population
v.
TRIUMPH-1 through TRIUMPH-5 — Phase 3 Clinical Programme
ClinicalTrials.gov · NCT05929066, NCT05882045, NCT05882110, NCT05536804, NCT05882045 · Ongoing trials with anticipated readouts 2026–2027
Available from Bangkok Peptides
Retatrutide, supplied locally in Thailand.
Bangkok Peptides supplies retatrutide as a research-grade peptide for laboratory use only. ≥99% HPLC/MS verified purity. Independent Janoshik Analytical reports per batch. Same-day Bangkok dispatch with tracked nationwide delivery across Thailand.
Vial Strengths
10 / 20 / 30mg
Purity
≥99% HPLC/MS
Dispatch
Same-Day Bangkok
From ฿3,800 · 10mg / 20mg / 30mg vial · For research use only
