Maximum Dose of Retatrutide
The maximum dose of retatrutide studied and used in clinical trials is 12 mg administered subcutaneously once weekly.
Dosing Information from Clinical Trials
The phase 2 clinical trials established the dosing range and maximum dose for retatrutide:
The 12 mg once-weekly dose represents the highest dose evaluated in both obesity and type 2 diabetes trials, with this dose initiated at a starting dose of 2 mg and escalated to the maintenance dose 1, 2.
In the type 2 diabetes trial, the 12 mg dose (with 2 mg starting dose) achieved HbA1c reductions of -2.02% at 24 weeks and bodyweight reductions of 16.94% at 36 weeks 1.
In the obesity trial, the 12 mg dose resulted in a mean bodyweight reduction of -24.2% at 48 weeks, with 100% of participants achieving ≥5% weight loss, 93% achieving ≥10% weight loss, and 83% achieving ≥15% weight loss 2.
Dose Escalation Strategy
The clinical trials utilized a dose escalation approach to minimize gastrointestinal side effects:
Starting doses of 2 mg were better tolerated than starting doses of 4 mg, with dose escalation occurring over several weeks to reach the target maintenance dose 1, 2.
The escalation strategy partially mitigated gastrointestinal adverse events (nausea, diarrhea, vomiting), which were the most common side effects and were dose-related 1, 2.
Safety Considerations at Maximum Dose
At the 12 mg dose, the safety profile remained consistent with other GLP-1 receptor agonists:
Gastrointestinal adverse events were mild to moderate in severity in most cases 1, 2.
Dose-dependent increases in heart rate peaked at 24 weeks (up to 6.7 beats/min) and declined thereafter, which requires monitoring in clinical practice 2, 3.
No severe hypoglycemia or deaths were reported in the phase 2 trials at any dose level 1, 2.
Serious adverse events at the 12 mg dose occurred in only 3% of participants in the body composition substudy 4.
Clinical Context
Retatrutide is administered as a subcutaneous injection once weekly, similar to other GLP-1 receptor agonists like semaglutide and dulaglutide 5.
Caution is recommended in patients with a history of medullary thyroid carcinoma, consistent with other GLP-1 receptor agonists 5.
The 12 mg dose demonstrated superior efficacy compared to lower doses (1 mg, 4 mg, 8 mg) in both glycemic control and weight reduction outcomes 1, 2.