Maximum Dose of Retatrutide
The maximum dose of retatrutide studied in humans is 12 mg administered subcutaneously once weekly.
Dosing Information from Clinical Trials
The highest dose of retatrutide evaluated across multiple phase 2 and phase 3 clinical trials has been 12 mg weekly 1, 2, 3. This represents the upper limit of dosing that has been systematically studied for both obesity and type 2 diabetes indications.
Key Dosing Details:
- Starting dose: 2 mg weekly (used in most escalation protocols)
- Maximum studied dose: 12 mg weekly
- Escalation strategy: Monthly dose increases from 2 mg baseline
- Route: Subcutaneous injection
- Frequency: Once weekly
- Half-life: Approximately 116.7 hours (allowing for weekly dosing)
Evidence from Clinical Trials
TRIUMPH-2 Trial (Type 2 Diabetes + Obesity)
The most recent phase 3 trial evaluated doses of 4 mg, 9 mg, and 12 mg weekly in adults with obesity and type 2 diabetes 1. At the 12 mg dose:
- Mean weight reduction: 18.8% at 80 weeks
- HbA1c reduction: Clinically significant improvements in glycemic control
- Completion rate: 84% of participants completed the study
Phase 2 Obesity Trial
In the landmark obesity trial, the 12 mg dose (starting at 2 mg) demonstrated 3:
- Weight reduction: 24.2% at 48 weeks
- 100% of participants achieved ≥5% weight loss
- 93% achieved ≥10% weight loss
- 83% achieved ≥15% weight loss
Phase 2 Type 2 Diabetes Trial
The diabetes-focused trial confirmed 12 mg as the maximum dose 2:
- HbA1c reduction: -2.02% at 24 weeks
- Weight reduction: 16.94% at 36 weeks
- Superior efficacy compared to dulaglutide 1.5 mg
Safety Profile at Maximum Dose
The 12 mg dose is associated with dose-dependent adverse effects, primarily gastrointestinal in nature 1, 3:
- Most common: Nausea (28%), diarrhea (34%), vomiting
- Severity: Predominantly mild to moderate
- Discontinuation rate: 8% due to adverse events at 12 mg dose
- Cardiovascular: Dose-dependent heart rate increases that peaked at 24 weeks and declined thereafter
- Other: Hypotension (6%) and dysesthesia (7%) more frequent than placebo
Important Caveats:
The gastrointestinal side effects are partially mitigated by starting at 2 mg rather than 4 mg, emphasizing the importance of gradual dose escalation 3. Permanent treatment discontinuation was higher at 9 mg (12%) compared to 12 mg (8%), suggesting that tolerability may be influenced more by escalation strategy than absolute dose 1.
Clinical Context
While 12 mg represents the maximum studied dose, doses of 8 mg and 12 mg showed comparable efficacy in several endpoints 3, 4. The 8 mg dose achieved:
- 22.8% weight reduction at 48 weeks
- 81.4% reduction in liver fat at 24 weeks
- 100% of participants achieving ≥5% weight loss
This suggests that the therapeutic ceiling may be reached before 12 mg for many patients, and the choice between 8 mg and 12 mg should balance efficacy gains against tolerability.
Practical Implications
No doses higher than 12 mg weekly have been evaluated in published clinical trials. The consistent use of 12 mg as the upper limit across multiple phase 2 and phase 3 studies 1, 2, 3, 4 indicates this represents both the maximum studied dose and likely the maximum clinically appropriate dose based on current evidence.