Does Retatrutide Come in Different Strengths?
Yes, retatrutide is being studied in multiple dose strengths ranging from 1 mg to 12 mg administered subcutaneously once weekly, with dose escalation strategies starting at 2 mg or 4 mg before reaching target maintenance doses. 1
Available Dose Strengths in Clinical Trials
Retatrutide has been evaluated in the following dose strengths:
- 1 mg once weekly 1
- 4 mg once weekly (with initial doses starting at either 2 mg or 4 mg) 1
- 8 mg once weekly (with initial doses starting at either 2 mg or 4 mg) 1
- 12 mg once weekly (with initial dose starting at 2 mg) 1
The medication has a mean half-life of approximately 6 days, which supports once-weekly subcutaneous dosing across all strength levels. 2
Dose-Response Relationship for Weight Loss
Higher doses demonstrate progressively greater weight loss efficacy:
- At 48 weeks, the 1 mg dose achieved 8.7% mean weight loss 1
- The 4 mg dose achieved 17.1% mean weight loss 1
- The 8 mg dose achieved 22.8% mean weight loss 1
- The 12 mg dose achieved 24.2% mean weight loss, compared to 2.1% with placebo 1
A meta-analysis confirmed dose-dependent improvements, with body weight reduction of 14.33% overall, and subgroup analyses showing increasing efficacy at 4 mg, 8 mg, and 12 mg doses. 3
Dose Titration Strategy
Starting with a lower initial dose (2 mg) before escalating to target maintenance doses partially mitigates gastrointestinal adverse events compared to starting at 4 mg. 1
The phase 2 trial specifically compared different escalation strategies:
- Starting at 2 mg before escalating to 4 mg, 8 mg, or 12 mg target doses
- Starting directly at 4 mg before escalating to target doses 1
The lower starting dose approach (2 mg) demonstrated better tolerability with reduced gastrointestinal side effects while maintaining efficacy. 1
Safety Profile Across Dose Strengths
Gastrointestinal adverse events (nausea, diarrhea, vomiting) are dose-related and mostly mild to moderate in severity. 1, 2
A critical dose-dependent cardiovascular effect occurs: heart rate increases peaked at 24 weeks (up to 6.7 beats/min at higher doses) and declined thereafter, though this may offset some cardiovascular benefits of weight loss. 1, 4
No significant difference in overall adverse event rates was observed between retatrutide and placebo groups (relative risk: 1.11, P = 0.24), though specific gastrointestinal events were more common with active treatment. 3
Current Regulatory Status
Retatrutide is not yet FDA-approved and remains investigational. 5, 2 It is being developed as an emerging triple-agonist therapy (GLP-1/GIP/glucagon receptor agonist) for obesity management. 5
The medication is positioned as a potential challenger to currently approved weight loss medications like semaglutide 2.4 mg and tirzepatide, though head-to-head comparator trials are notably absent from the current development program. 4