Weight management, metabolic health, glucose regulation
GLP-3 (Retatrutide)
Retatrutide (LY3437943), informally called “GLP-3” or “R3ta” is an investigational triple receptor agonist targeting GIP, GLP-1, and glucagon receptors. It is being studied for obesity, type 2 diabetes, and metabolic liver disease.
Administration Reference
Subcutaneous
Source / Evidence Context
Human study protocol
Dose Information
Minimum viable dosing: 1mg -12mg increasing .5mg as hunger returns or extended
Frequency
Once weekly on a consistent schedule.
Duration / Cycle
Ongoing; no fixed end date
Storage Guidance
Refrigerate after reconstitution and use within approximately 30 days, Freeze for lyophilized powder form
Supplies
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Listings are not a required kit or confirmation of suitability for a particular peptide, formulation, or route. Check the product specifications and intended use.
Syringes & transfer supplies
EasyTouch U-100 Insulin Syringes (31G 0.5cc 5/16″) – 100ct.U-100 Insulin Syringes (31G 0.5cc 5/16") – 100ctInsulin syringes – Polybag, 50 Unit Capacity, 5/16” Needle Length, Bold Markings for Accurate Dosing, Disposable, Box of 100View at AMAZON →
Protective supplies & disposal
MED PRIDE Sterile Alcohol Prep Pads1 BOX OF 200INDIVIDUALLY WRAPPED ISOPROPYL ALCOHOL WIPES, PACK OF 1 BOX OF 200, MEDIUM SIZE PREP PADSView at AMAZON →
Inspire Black Nitrile Gloves HEAVY DUTY 6 Mil100ctView at AMAZON →
Square Sharps Container, 2 QuartQTY 1View at AMAZON →
Commonly Reported Uses
Weight management; appetite regulation; type 2 diabetes research; glucose control; insulin sensitivity; metabolic health; liver-fat reduction; cardiometabolic risk-factor improvement.
Commonly Reported Indicators
Reduced appetite and food cravings, smaller portion sizes, progressive weight reduction, improved glucose control and HbA1c, reduced waist circumference, and improvements in liver fat, triglycerides, cholesterol, and blood pressure in clinical research.
Mechanism Overview
Retatrutide simultaneously activates GLP-1, GIP, and glucagon receptors. GLP-1 and GIP signaling contribute to glucose-dependent insulin secretion, appetite reduction, and satiety, while glucagon-receptor activation is intended to increase energy expenditure and fat metabolism.
Safety
Safety Considerations
Clinical studies report a dose-dependent safety profile dominated by gastrointestinal effects, particularly during dose escalation. Published Phase 2 obesity research also observed dose-dependent increases in heart rate that peaked around 24 weeks and subsequently declined. The source additionally highlights pancreatitis, gallbladder problems, severe hypoglycemia, excessive weight loss, and severe renal impairment as important concerns.
Reported Adverse Effects
Nausea, diarrhea, constipation, vomiting, and other gastrointestinal symptoms, particularly during dose escalation. Dysesthesia, including tingling or burning sensations, has also been reported, particularly at higher doses.
Contraindications & Cautions
Personal or family history of medullary thyroid carcinoma; MEN2 syndrome; severe renal impairment. Additional caution is warranted for symptoms suggestive of pancreatitis, gallbladder disease, severe hypoglycemia, persistent vomiting, or excessive weight loss.
Status
Regulatory Status
Retatrutide is not FDA approved and remains an investigational compound in clinical development. Products marketed online as “GLP-3,” “GLP-3R,” or retatrutide research peptide are not FDA-approved pharmaceutical products for human use.
Development / Research Status
Investigational clinical compound
Market Classification
Research-use compound
Status Notes
Retatrutide is in late-stage clinical development, including Phase 3 programs for obesity and related metabolic conditions. “GLP-3” is an informal marketing/media label rather than an official endogenous hormone designation.
Research & Evidence
Research Last Reviewed
2026-09-05
Research Overview
Retatrutide has Phase 2 human clinical evidence in obesity and type 2 diabetes, a Phase 2a substudy examining metabolic dysfunction-associated steatotic liver disease, and structural research characterizing its simultaneous activity at GLP-1, GIP, and glucagon receptors. Phase 3 development is ongoing.
Human Research
A Phase 2 obesity trial enrolled 338 adults and evaluated once-weekly subcutaneous retatrutide for 48 weeks. Mean weight reduction at 48 weeks reached 24.2% with the 12 mg dose and 22.8% with 8 mg, versus 2.1% with placebo. A separate Phase 2 trial in 281 people with type 2 diabetes demonstrated dose-dependent reductions in HbA1c and body weight. In a 98-participant MASLD substudy, liver fat decreased by 82.4% at 24 weeks with 12 mg retatrutide, and 86% of that group achieved liver-fat content below 5%.
In Vitro Research
Structural and receptor-level research demonstrates simultaneous activation of GLP-1R, GIPR, and GCGR by retatrutide and helps characterize the molecular basis of its triple-agonist activity.
References
Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. PMID: 37366315. DOI: 10.1056/NEJMoa2301972.
Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomized, double-blind, placebo- and active-controlled phase 2 trial. Lancet. 2023;402(10401):529-544. PMID: 37385280. DOI: 10.1016/S0140-6736(23)01053-X.
Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30(7):2037-2048. PMID: 38858523. DOI: 10.1038/s41591-024-03018-2.
Li W, Zhou Q, Cong Z, et al. Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide. Cell Discov. 2024;10(1):77. PMID: 39019866. DOI: 10.1038/s41421-024-00700-0.
Urva S, Coskun T, Loh MT, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomized, multiple-ascending dose trial. Lancet. 2022;400(10366):1869-1881. PMID: 36354040. DOI: 10.1016/S0140-6736(22)02033-5.
Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. 2022;34(9):1234-1247.e9. PMID: 35985340. DOI: 10.1016/j.cmet.2022.07.013.
Marathe SJ, Grey EW, Bohm MS, et al. Incretin triple agonist retatrutide (LY3437943) alleviates obesity-associated cancer progression. NPJ Metab Health Dis. 2025;3(1):10. PMID: 40094000. DOI: 10.1038/s44324-025-00054-5.
ClinicalTrials.gov. TRIUMPH-1: A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight. NCT05929066. Phase 3.
ClinicalTrials.gov. TRIUMPH-2: A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight. NCT05929079. Phase 3.
ClinicalTrials.gov. TRIUMPH-3: A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease. NCT05882045. Phase 3.
ClinicalTrials.gov. TRIUMPH-Outcomes: The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obesity. NCT06383390.