Retatrutide is a powerful triple agonist peptide that targets GLP-1, GIP (glucose-dependent insulinotropic polypeptide), and glucagon receptors—making it the most comprehensive metabolic peptide in its class. It builds on the progress of earlier compounds like Semaglutide and Tirzepatide by activating three key hormonal pathways involved in appetite regulation, glucose control, and fat metabolism.
This enhanced activity leads to faster, more dramatic fat loss while offering additional therapeutic effects across multiple body systems.
Mechanism of Action
- GLP-1 Receptor Agonism: Slows gastric emptying, reduces appetite, regulates insulin secretion
- GIP Receptor Agonism: Enhances insulin release, improves glucose tolerance, improves fat metabolism
- Glucagon Receptor Agonism: Stimulates energy expenditure and promotes fat breakdown (lipolysis)
Clinical Effectiveness
- Semaglutide (GLP-1 only): 17% average body weight loss after 68 weeks
- Tirzepatide (GLP-1 + GIP): 24.7% body weight loss after 72 weeks
- Retatrutide (GLP-1 + GIP + Glucagon):
- 17.5% average weight loss in just 24 weeks
- 26.2% average loss in only 48 weeks
This rapid and sustained weight reduction places Retatrutide as the most effective peptide currently being studied for metabolic disorders and fat loss.
Additional Benefits
- Anti-inflammatory: May assist with autoimmune conditions such as rheumatoid arthritis and inflammatory bowel disease
- Collagen Support: Promotes epithelialization and collagen synthesis, enhancing skin tone and elasticity
- Wound Healing: Accelerates post-injury tissue regeneration
- Angiogenesis: Encourages the formation of new blood vessels to improve circulation and tissue oxygenation
- Muscle Regeneration: Activates satellite cells for muscle growth and repair
Emerging Therapeutic Applications
Beyond weight loss and glucose control, Retatrutide is being explored for a wide array of research purposes:
- Cardiovascular Health: May reduce risk factors like hypertension, cholesterol imbalance, and vascular inflammation
- Liver Health: Shows promise for reversing non-alcoholic fatty liver disease (NAFLD)
- Neurological Disorders: Under investigation for Parkinson’s, Alzheimer’s, and other neurodegenerative diseases
- Sleep & Addiction: Potential role in treating sleep apnea, substance use disorders, and depression
Possible Side Effects
Common (Mild to Moderate):
- Nausea
- Vomiting
- Headache
- Indigestion
- Constipation or diarrhea
- Abdominal discomfort
- Dehydration
Rare but Serious:
- Gallbladder issues (e.g., gallstones)
- Pancreatitis
- Severe allergic reaction
- Intestinal blockages
- Gastroparesis (delayed stomach emptying)
- Dehydration-induced kidney strain (especially in those with existing kidney disease)
Important: Most side effects are dose-dependent and time-dependent. Higher doses over long durations increase risk. These effects can be minimized with proper stacking, hydration, and dosage planning.
Side Effect Management Tips
- Avoid fatty or greasy foods
- Maintain consistent hydration
- Stop eating once full — satiety occurs earlier on GLP-1/GIP peptides
- Dose at night
- Use fiber supplements to avoid constipation
- If the standard dosing protocol causes you too many side effects, it can be amended to allow you to start at less than the typical dose, and to increase gradually in smaller increments rather than following the 2mg increase all at once after 4 weeks. Consult staff for assistance
Contraindications
Do NOT use Retatrutide if…
- You are pregnant or nursing
- You have chronic kidney disease
- You have advanced liver disease
- You have severe gastrointestinal disorders, such as Crohn’s or IBD
- You or a family member has a history of thyroid cancer
- You are allergic or hypersensitive to peptide-based medications
Reconstitution and Dosing Protocols
General Guidelines
- Dose once every 7 days, always on the same day of the week.
- Remain at each dose for a minimum of 4 weeks; if you are losing at your current dose, you may remain at that dose until you must increase the dose to continue losing weight.
- Dose at night if you are experiencing adverse side effects.
- Subcutaneous Administration
Determining your starting dose:
-If you have no history on GLP’s, start at 2mg
-If you have been on a GLP for long enough to have increased your dose once, start at 4mg
Stacking Suggestions
Retatrutide can be strategically stacked to overcome plateaus, protect muscle tissue, and accelerate body composition changes:
- AOD-9604 – Increases lipolysis and preserves muscle during weight loss
- BPC-157 & TB-500 – Enhance healing, especially for soft tissue and joint inflammation common during weight loss
- GHKCU – For collagen production, skin tightening, and post-fat loss regeneration
- Semax / Selank – To support mental clarity, mood, and prevent brain fog associated with appetite suppression
- Glutathione – For detox support and liver optimization
- LIPO-C – To enhance energy and fat breakdown when paired with metabolic peptides
