Retatrutide Research Information
GLP-1 / GIP / Glucagon Receptor Agonist
Triple Hormone Receptor Agonist for Metabolic Research
Important: This information is for educational and research purposes only. Always consult with a qualified healthcare professional before use.
Contents
What is Retatrutide?
Retatrutide (LY3437943) is a novel single-molecule triple hormone receptor agonist that targets three key receptors involved in metabolic regulation. It is the first investigational agent to combine GLP-1, GIP, and glucagon receptor agonism in a single peptide [citation:6][citation:9].
- GLP-1 receptor – Regulates appetite and insulin secretion
- GIP receptor – Enhances insulin sensitivity
- Glucagon receptor – Increases energy expenditure and fat metabolism
This triple-agonist approach is distinct from other medications in its class. Unlike semaglutide which activates only the GLP-1 receptor, or tirzepatide which activates GLP-1 and GIP, retatrutide uniquely targets all three receptors [citation:6].
How Retatrutide Works
Retatrutide mimics three naturally occurring hormones that regulate appetite, blood sugar, and energy balance [citation:6]:
GLP-1
Reduces appetite, slows digestion, enhances insulin secretion
GIP
Improves insulin sensitivity, supports metabolic health
Glucagon
Increases energy expenditure, promotes fat metabolism [citation:9]
The addition of glucagon agonism is what sets retatrutide apart. Glucagon works on the "output" side of metabolism by increasing fat oxidation and energy expenditure, rather than just reducing food intake [citation:9]. Combined, these mechanisms promote reduced food intake, improved insulin response, and increased calorie burning.
Research Applications
Retatrutide has been studied across multiple clinical trials, with research focusing on [citation:1][citation:5][citation:7]:
Obesity & Weight Management
Evaluated for weight reduction in individuals with obesity or overweight. Phase 3 TRIUMPH trials demonstrated up to 28-29% mean weight loss at 12 mg dose [citation:1][citation:7].
Type 2 Diabetes
TRANSCEND-T2D-1 trial demonstrated significant reductions in both A1C and body weight [citation:8].
Cardiometabolic Health
Significant improvements in blood pressure, lipids, waist circumference, and liver fat. Dramatic reductions in liver fat observed with many returning to normal levels [citation:9].
Metabolic Research
Investigating effects on metabolic dysfunction-associated steatotic liver disease (MASLD), osteoarthritis, and sleep apnea [citation:7].
Clinical Studies
Phase 2 Trial (Jastreboff et al., NEJM 2023)
In a Phase 2 trial involving adults with obesity or overweight, retatrutide demonstrated substantial weight loss at 48 weeks [citation:1][citation:10]:
| Dose | Weight Loss at 24 Weeks | Weight Loss at 48 Weeks |
|---|---|---|
| 1 mg | −7.2% | −8.7% |
| 4 mg | −12.9% | −17.1% |
| 8 mg | −17.3% | −22.8% |
| 12 mg | −17.5% | −24.2% |
| Placebo | −1.6% | −2.1% |
Key finding: At the 12 mg dose, participants lost an average of 24.2% of their body weight after 48 weeks [citation:1][citation:10].
Phase 3 TRIUMPH Trials
The Phase 3 TRIUMPH program has demonstrated even more impressive results [citation:1][citation:7]:
- TRIUMPH-1: 12 mg dose produced average weight loss of 28.3% (70.3 lbs) over 80 weeks [citation:8]
- TRIUMPH-4: 12 mg dose produced average weight loss of 28.7% (71 lbs) over 68 weeks in adults with obesity and knee osteoarthritis [citation:7]
- TRIUMPH-1 (4 mg): Even the lower 4 mg dose produced average weight loss of 19% over 80 weeks [citation:1]
Interactive Dosing Guide
Select your pen size and dose to see the corresponding volume, clicks, dosing frequency, and how many doses per pen:
Step 1: Select Your Pen Size
Step 2: Select Your Dose
Pen Size
20mg Pen
Selected Dose
2 mg
Doses per Pen
10 doses
Pen Clicks
30 clicks
Volume
0.30 mL
Protocol Level
Level 1
Recommended Schedule
Once weekly - Loading Phase (Weeks 1-4)
Do not change your dose unless advised by a qualified professional.
Protocol Level Summary
Based on Phase 3 clinical trial protocols [citation:1][citation:5]:
| Protocol Level | Target Dose | Frequency | Pen Clicks | Who It's For |
|---|---|---|---|---|
| Level 1 (Starting) | 2 mg | Once weekly | 20-40 clicks | New users, weeks 1-4 |
| Level 2 (Loading) | 4 mg | Once weekly | 40-80 clicks | Weeks 5-8 |
| Level 3 (Intermediate) | 6-8 mg | Once weekly | 60-120 clicks | Weeks 9-12 |
| Level 4 (Maintenance) | 9-12 mg | Once weekly | 90-180 clicks | Week 13+ maintenance |
Do not change your dose unless advised by a qualified professional.
Vial Users (Insulin Syringe)
Add 3mL of bacteriostatic water to your freeze-dried vial and mix gently. After reconstitution, use the table below to draw your dose:
Vial Size
20mg vial with 3mL bac water
| Dose | Units on Syringe | Volume (mL) | Protocol Level |
|---|
Always use a new sterile needle and syringe for each injection.
Safety & Precautions
Do not use if you [citation:4][citation:11]:
- Have a personal or family history of medullary thyroid carcinoma (MTC) or MEN-2 syndrome
- Are allergic to retatrutide or any ingredients
- Have type 1 diabetes
- Are pregnant or breastfeeding
- Have a history of recurrent or severe hypoglycemia
Common side effects [citation:4][citation:11]:
- Nausea (most common)
- Diarrhea
- Decreased appetite
- Vomiting
- Constipation
- Indigestion (dyspepsia)
- Abdominal pain
Warning: If you experience severe and ongoing abdominal pain (which may spread to the back), persistent vomiting, difficulty breathing, signs of an allergic reaction (hives, swelling of face/lips/tongue/throat), or jaundice, seek immediate medical help [citation:4][citation:11].
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. [citation:1]
- Rosenstock J, et al. "Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes." The Lancet. 2023;402:529-544.
- TRIUMPH-1 Trial Results. Eli Lilly and Company. 2025. [citation:1][citation:8]
- TRIUMPH-4 Trial Results. Eli Lilly and Company. 2025. [citation:7]
- ClinicalTrials.gov. "A Study of Retatrutide (LY3437943) in Participants With Obesity or Overweight." NCT04881760.
- DailyMed Label: RETATRUTIDE PEN injection, solution. NIH. 2025. [citation:4]
This information is for educational and research purposes only. Always consult with a qualified healthcare professional.
Last updated: August 2026