RESEARCH PROFILE
RETATRUTIDE
Triple GIP, GLP 1 & Glucagon Receptor Agonist
Retatrutide, also known as LY3437943, is an investigational peptide designed to activate three metabolic hormone receptors within a single molecule: GIP, GLP 1, and glucagon. It is being studied in Phase 3 clinical development for obesity, type 2 diabetes, and several obesity related conditions. Lilly
INVESTIGATIONAL • PHASE 3 CLINICAL DEVELOPMENT • NOT FDA APPROVED
RETATRUTIDE AT A GLANCE
Category
Triple hormone receptor agonist
Alternate Name
LY3437943
Primary Targets
GIP • GLP 1 • Glucagon
Research Stage
Phase 3 clinical development
Regulatory Status
Investigational • Not FDA approved
Human Evidence
Phase 1, Phase 2, and Phase 3 clinical research
The FDA states that retatrutide is not a component of any FDA approved drug and has not been found safe and effective by FDA for any condition. U.S. Food and Drug Administration
WHAT IS RETATRUTIDE?
Retatrutide is a synthetic peptide developed by Eli Lilly as a single molecule capable of activating the receptors for glucose dependent insulinotropic polypeptide (GIP), glucagon like peptide 1 (GLP 1), and glucagon.
These signaling systems are involved in metabolic regulation, including appetite, glucose metabolism, energy balance, and nutrient handling.
Unlike medications that target GLP 1 alone or GIP and GLP 1 together, retatrutide adds glucagon receptor activity to create a three receptor approach. Researchers are investigating whether this combination can produce distinct metabolic effects beyond those achieved by targeting fewer pathways.
MECHANISM OF ACTION
Retatrutide simultaneously activates three hormone receptor systems.
GIP RECEPTOR
GIP is an incretin hormone involved in insulin secretion and nutrient metabolism. Retatrutide activates the GIP receptor as one component of its metabolic signaling profile.
GLP 1 RECEPTOR
GLP 1 receptor activation influences appetite and satiety, glucose dependent insulin secretion, glucagon signaling, and gastric function.
GLUCAGON RECEPTOR
Glucagon signaling plays an important role in hepatic glucose regulation and energy metabolism. Researchers are studying whether adding glucagon receptor activity to incretin signaling may influence energy expenditure and substrate utilization.
The combined activity of these three pathways is the defining feature of retatrutide and the reason it is frequently described as a triple hormone receptor agonist.
WHAT THE RESEARCH SHOWS
PHASE 2 HUMAN EVIDENCE
A randomized, double blind, placebo controlled Phase 2 trial published in The New England Journal of Medicine studied 338 adults with obesity or overweight plus a weight related condition.
At 48 weeks, mean body weight changes were:
1 mg: −8.7%
4 mg: −17.1%
8 mg: −22.8%
12 mg: −24.2%
Placebo: −2.1%
In the 12 mg group, 83% of participants achieved at least 15% weight reduction during the 48 week trial.
The investigators noted that weight reduction had not clearly plateaued by the end of the study. New England Journal of Medicine
PHASE 3 EVIDENCE
Retatrutide subsequently advanced into the large TRIUMPH Phase 3 clinical development program.
In TRIUMPH 1, Lilly reported that participants receiving 12 mg retatrutide experienced an average 28.3% body weight reduction over 80 weeks in the efficacy analysis. Eli Lilly and Company
In the earlier TRIUMPH 4 Phase 3 trial involving participants with obesity or overweight and knee osteoarthritis, the 12 mg group experienced an average 28.7% reduction in body weight at 68 weeks, compared with 2.1% for placebo. Improvements in knee pain and physical function were also reported. Eli Lilly and Company
Phase 3 research has also evaluated retatrutide in people with type 2 diabetes, obstructive sleep apnea, cardiovascular disease, and other obesity related conditions. Eli Lilly and Company
IMPORTANT EVIDENCE LIMITATIONS
Retatrutide remains investigational.
Some of the newer Phase 3 findings are currently available as sponsor announced topline results or scientific presentations rather than complete peer reviewed publications. Those findings should therefore be distinguished from the published Phase 2 evidence.
Long term safety, durability of effects, cardiovascular outcomes, and the complete benefit risk profile remain subjects of ongoing clinical investigation. Lilly
SAFETY & RESEARCH CONSIDERATIONS
Clinical trials provide meaningful human safety information, but retatrutide's complete safety profile has not yet been established through regulatory approval.
COMMONLY REPORTED
In the published Phase 2 obesity trial, gastrointestinal adverse events were the most frequently reported.
These were generally dose related and predominantly mild to moderate in severity.
Reported gastrointestinal effects included symptoms such as:
Nausea
Diarrhea
Vomiting
Constipation
Lower starting doses reduced some gastrointestinal effects during dose escalation. New England Journal of Medicine
HEART RATE
Dose dependent increases in heart rate were observed during the Phase 2 trial. These increases peaked around week 24 and subsequently declined. New England Journal of Medicine
CONTINUING SAFETY RESEARCH
Because retatrutide remains investigational, its long term safety profile continues to be evaluated in Phase 3 trials.
Research findings should not be interpreted as establishing safety for unsupervised or non trial use.
REGULATORY CONTEXT
RETATRUTIDE IS NOT FDA APPROVED
Retatrutide remains an investigational drug.
The FDA states that retatrutide:
Is not a component of an FDA approved drug
Has not been found safe and effective by FDA for any condition
Cannot be used in human drug compounding under federal law
FDA has taken enforcement action involving the marketing and distribution of unapproved retatrutide products and active pharmaceutical ingredient intended for compounding. U.S. Food and Drug Administration
Lilly similarly states that retatrutide has not been approved by any regulatory agency and remains under clinical investigation. Lilly
Research status matters. Clinical trial findings do not constitute regulatory approval and should not be interpreted as individualized medical guidance.
ANALYTICAL DOCUMENTATION
Croix maintains available third party analytical documentation for specific samples and lots represented in its research library.
RETATRUTIDE 10 MG
Laboratory
Optiq Health Labs
Lot
dptx81926r10
Sample ID
1264.OPT.260910
Report Date
September 18, 2026
Reported Net Content
10.22 mg/vial
Reported Purity
99.5%
Identity
LC MS confirmation • Tested
Endotoxin
Pass
Sterility
Pass
RETATRUTIDE 30 MG
Laboratory
Optiq Health Labs
Lot
kizn072426
Sample ID
1266.OPT.260910
Report Date
September 18, 2026
Reported Net Content
29.84 mg/vial
Reported Purity
99.7%
Identity
LC MS confirmation • Tested
Endotoxin
Pass
Sterility
Pass
IMPORTANT COA LIMITATION
Analytical results apply only to the specific sample identified in the corresponding laboratory report.
A Certificate of Analysis for one sample does not establish the composition, purity, sterility, safety, efficacy, or characteristics of another sample, lot, batch, or product. The laboratory specifically limits its reported findings to the sample it received and tested. COAs-2(2)
SELECTED RESEARCH & REFERENCES
Jastreboff AM, et al.
Triple Hormone Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial.
New England Journal of Medicine. 2023;389:514–526.
DOI: 10.1056/NEJMoa2301972
View Published Study
TRIUMPH 1 — Phase 3
ClinicalTrials.gov Identifier: NCT05929066
Phase 3 evaluation of retatrutide in adults with obesity or overweight. ClinicalTrials.gov
U.S. Food & Drug Administration
FDA's Concerns with Unapproved GLP 1 Drugs Used for Weight Loss.
View FDA Information
Eli Lilly and Company
Retatrutide clinical development and research information. Lilly
RESEARCH & EDUCATIONAL INFORMATION
This profile is provided for research and educational reference. It does not constitute individualized medical advice or establish that an investigational compound is safe or effective for personal use.
Retatrutide is investigational and is not FDA approved. Evidence continues to evolve as additional clinical trials are completed, presented, peer reviewed, and evaluated by regulatory authorities.
Analytical documentation presented by Croix applies only to the specific samples and lots identified in the corresponding laboratory reports.