Retatrutide Dosing for Weight Loss
Retatrutide is typically initiated at 2 mg once weekly by subcutaneous injection, with gradual dose escalation to a target maintenance dose of 8-12 mg weekly, which provides the most significant weight loss benefits of 22.8-24.2% at 48 weeks. 1
Dosing Protocol and Escalation Schedule
Retatrutide follows a specific dose escalation protocol to minimize gastrointestinal side effects while maximizing efficacy:
- Starting dose: 2 mg subcutaneously once weekly
- Dose escalation: Gradual increases every 4 weeks
- Escalation pathway: 2 mg → 4 mg → 8 mg → 12 mg
- Target maintenance dose: 8-12 mg weekly (provides optimal weight loss)
The slow escalation approach (starting at 2 mg rather than 4 mg) has been shown to partially mitigate gastrointestinal adverse events while maintaining efficacy 1.
Efficacy by Dose
Clinical trial data demonstrates clear dose-dependent weight loss with retatrutide at 48 weeks 1:
- 1 mg weekly: 8.7% weight loss
- 4 mg weekly: 17.1% weight loss
- 8 mg weekly: 22.8% weight loss
- 12 mg weekly: 24.2% weight loss
These results significantly outperform placebo (2.1% weight loss) and are superior to other GLP-1 receptor agonists like liraglutide (8.0% at 56 weeks) 2.
Response Assessment
- Evaluate efficacy at 24 weeks after reaching maintenance dose
- If inadequate weight loss is achieved (typically <5% from baseline), consider discontinuation or dose adjustment
- Continue monitoring every 12 weeks thereafter
Common Side Effects and Management
The most common adverse events are gastrointestinal in nature, similar to other GLP-1 receptor agonists 1:
- Nausea
- Diarrhea
- Vomiting
- Constipation
These side effects are typically dose-related, mild to moderate in severity, and can be partially mitigated with the lower starting dose and gradual titration schedule 1.
Monitoring Requirements
- Regular assessment of weight loss response
- Monitoring for gastrointestinal side effects
- Heart rate monitoring (dose-dependent increases that peak at 24 weeks and decline thereafter) 1
- Assessment for potential complications such as pancreatitis or gallbladder disease
Comparison to Other GLP-1 Receptor Agonists
Retatrutide is a triple agonist targeting GLP-1, GIP, and glucagon receptors, distinguishing it from dual agonists like tirzepatide or single GLP-1 receptor agonists like semaglutide and liraglutide 3. This triple mechanism appears to provide enhanced weight loss efficacy:
- Retatrutide 12 mg: 24.2% weight loss at 48 weeks 1
- Tirzepatide 15 mg: 20.9% weight loss at 72 weeks 4
- Semaglutide 2.4 mg: 14.9-16.0% weight loss at 68 weeks 4
- Liraglutide 3.0 mg: 8.0% weight loss at 56 weeks 2
Important Considerations
- Retatrutide is still investigational and not yet FDA-approved for weight management
- Long-term therapy will likely be necessary as significant weight regain typically occurs after discontinuation of GLP-1 receptor agonists 4
- Combination with lifestyle modifications (reduced-calorie diet and physical activity) is recommended for optimal results
- The medication is administered as a subcutaneous injection once weekly
Potential Contraindications
Based on similar medications in this class, potential contraindications may include:
- Pregnancy or breastfeeding
- Personal or family history of medullary thyroid carcinoma
- Multiple endocrine neoplasia syndrome type 2
- History of pancreatitis
The impressive weight loss results with retatrutide, particularly at the 8-12 mg doses, suggest it may become an important addition to obesity management once approved.