Retatrutide
Triple GLP-1/GIP/Glucagon Agonist | Weight Loss & Diabetes
Novel triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors. Phase II trials demonstrated 24.2% weight loss at 48 weeks—the highest recorded for obesity medications.
Mechanism of Action
Activates GLP-1 for appetite suppression, GIP for insulin sensitivity, and glucagon for increased energy expenditure and hepatic fat oxidation.
Key Benefits
- Superior weight loss (24.2% at 48 weeks)
- Improved glycemic control (HbA1c reduction up to 2.16%)
- Enhanced cardiovascular benefits
- Hepatic fat reduction (up to 82%)
- Triple mechanism addresses obesity through multiple pathways
HUEGTFTSDVSSYLEGQAAKEFIAWLVRGRGPSSGAPPPSHistidine
Position 1
Aminoisobutyric Acid
Position 2
Glutamic Acid
Position 3
Glycine
Position 4
Threonine
Position 5
Phenylalanine
Position 6
Threonine
Position 7
Serine
Position 8
Aspartic Acid
Position 9
Valine
Position 10
Serine
Position 11
Serine
Position 12
Tyrosine
Position 13
Leucine
Position 14
Glutamic Acid
Position 15
Glycine
Position 16
Glutamine
Position 17
Alanine
Position 18
Alanine
Position 19
Lysine
Position 20
Glutamic Acid
Position 21
Phenylalanine
Position 22
Isoleucine
Position 23
Alanine
Position 24
Tryptophan
Position 25
Leucine
Position 26
Valine
Position 27
Arginine
Position 28
Glycine
Position 29
Arginine
Position 30
Glycine
Position 31
Proline
Position 32
Serine
Position 33
Serine
Position 34
Glycine
Position 35
Alanine
Position 36
Proline
Position 37
Proline
Position 38
Proline
Position 39
Serine
Position 40
Weight Loss
- Superior Weight Reduction
Clinical trials show 17.5% weight loss at 24 weeks and 24.2% at 48 weeks.
- Sustained Weight Management
Continuous weight loss with no plateau at 48 weeks suggests greater long-term potential.
- Triple Mechanism
Addresses obesity through appetite suppression, energy expenditure, and metabolic efficiency.
Type 2 Diabetes
- Superior Glycemic Control
HbA1c reductions up to 2.16% with 82% achieving target levels below 6.5%.
- Glucose-Dependent Regulation
Balanced glycemic control with minimal hypoglycemia risk.
- Insulin Sensitivity
Marked improvements in sensitivity with potential for reduced exogenous insulin requirements.
Cardiovascular/Metabolic
- Lipid Improvement
Non-HDL cholesterol reductions up to 26.9%, triglyceride reductions up to 40.6%.
- Blood Pressure Optimization
Consistent decreases in systolic and diastolic blood pressure across trials.
- Hepatic Fat Reduction
Up to 82% reduction in liver fat with normalization in 90% of participants.
Weekly subcutaneous injection into abdomen, thigh, or upper arm with site rotation.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Starting Dose (Week 1-4) | 0.5mg | Once weekly | SubQ |
| Low Maintenance (Week 4-8) | 1mg | Once weekly | SubQ |
| Escalation (Week 8-12) | 2mg | Once weekly | SubQ |
| Moderate (Week 12-16) | 4mg | Once weekly | SubQ |
| Advanced (Week 16-20) | 8mg | Once weekly | SubQ |
| Maximum Efficacy (Week 20+) | 12mg | Once weekly | SubQ |
Reconstitution Instructions
- Sterile bacteriostatic water for injection
- Lyophilized Retatrutide vial
- Insulin syringes (0.3-1mL capacity)
- Alcohol swabs
- Sharps disposal container
- 1 Allow vial to reach room temperature (15-20 minutes)
- 2 Clean vial top with alcohol swab and air dry completely
- 3 Add calculated bacteriostatic water slowly down vial side
- 4 Gently swirl in circular motions—avoid vigorous shaking
- 5 Allow full dissolution (2-3 minutes); solution should be clear and colorless
- 6 Store reconstituted solution refrigerated at 2-8°C for up to 28 days
- 7 Inject subcutaneously; rotate sites weekly
Do not combine with other dual/triple agonists—risk of severe hypoglycemia and excessive GI effects.
Do not combine—overlapping GLP-1 agonist mechanisms increase severe hypoglycemia risk.
Both cause significant GI effects. Not recommended without specialist supervision.
May significantly reduce insulin requirements. Monitor blood glucose and adjust insulin doses accordingly.
Safe combination tested in clinical trials. Different mechanisms work complementarily for glucose control.
Clinical trials included SGLT2 inhibitors with no safety concerns.
Safe combination; BPC-157 may provide GI protective benefits during retatrutide use.
Space oral contraceptives by 1 hour before retatrutide due to delayed gastric emptying.
Initial appetite suppression and mild GI effects as body adapts to triple hormone activation
Noticeable food cravings reduction and portion size decrease; early weight loss (2-5%)
Significant appetite control and steady weight loss (5-10%); improved glucose control
Substantial weight reduction (10-18%) with enhanced energy expenditure
Major weight loss milestone (15-22%) with cardiovascular benefits and liver fat reduction
Maximum clinical efficacy (20-24.2%) with comprehensive metabolic improvements
Common Side Effects
- Gastrointestinal effects (nausea, vomiting, diarrhea)—typically mild to moderate
- Heart rate increases—common especially in first 24 weeks
- Appetite suppression
- Mild dehydration
Stop Signs - Discontinue if:
- Severe persistent nausea or vomiting preventing adequate nutrition
- Signs of pancreatitis: severe abdominal pain radiating to back
- Severe hypoglycemia symptoms: confusion, dizziness, sweating
- Excessive weight loss (>3 lbs per week consistently or >25% total body weight)
- Gallbladder problems: severe right upper abdominal pain
Contraindications
- Personal or family history of medullary thyroid carcinoma
- MEN2 syndrome
- Severe renal impairment
Good Signs
- Pharmaceutical-grade white powder with uniform texture
- Proper cold chain maintenance (2-8°C refrigeration)
- Clear, colorless reconstituted solution without particles
- Stable extended half-life effects (consistent appetite suppression between doses)
Warning Signs
- Source verification critical—counterfeit versions circulate due to investigational status
Bad Signs
- Rapid tolerance or effectiveness loss suggests degraded or counterfeit product
- Unusual side effect profile may indicate contamination
- Phase II Obesity Trial(2023)
Landmark RCT in 338 participants showing dose-dependent weight loss; 12mg dose achieved 24.2% reduction—highest recorded for any obesity medication. NEJM.
- Phase II Type 2 Diabetes Study(2023)
Trial in 281 participants with type 2 diabetes: 16.9% weight loss and HbA1c reductions up to 2.16%. The Lancet.
- MASLD Substudy(2024)
Metabolic dysfunction-associated steatotic liver disease study: 82% liver fat reduction with normalization in >90% at highest doses. Nature Medicine.
- Structural Insights into Triple Agonism(2024)
Cryo-EM structures reveal simultaneous activation of GLP-1R, GIPR, and GCGR, explaining superior clinical efficacy. Cell Discovery.
Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.