Initial Dose of Retatrutide
The initial dose of retatrutide is 2 mg subcutaneously once weekly, which serves as the starting dose before escalating to higher maintenance doses of 4 mg, 8 mg, or 12 mg. 1, 2
Dosing Strategy and Escalation
Retatrutide requires dose escalation to minimize gastrointestinal side effects, with the 2 mg starting dose used for 4 weeks before increasing to higher maintenance doses. 1, 2
The phase 2 obesity trial demonstrated that starting with 2 mg (rather than 4 mg) partially mitigated gastrointestinal adverse events, which were dose-related and mostly mild to moderate in severity. 1
For the 4 mg maintenance dose, participants started at 2 mg for the initial period before escalating. 1
For the 8 mg maintenance dose, two escalation strategies were tested: starting at either 2 mg or 4 mg, both showing similar efficacy. 1, 2
For the 12 mg maintenance dose, the starting dose was 2 mg with gradual escalation over the treatment period. 1, 2
Administration Details
Retatrutide is administered as a subcutaneous injection once weekly at any time, regardless of meals. 1, 2
The medication is given for extended treatment periods (24-48 weeks in clinical trials) to achieve maximal weight loss and metabolic benefits. 1, 2
Clinical Context
In the phase 2 obesity trial, participants had either a BMI ≥30 kg/m² or BMI 27-<30 kg/m² with at least one weight-related condition. 1
For type 2 diabetes, participants had HbA1c of 7.0-10.5% and BMI of 25-50 kg/m², with the same 2 mg starting dose strategy. 2
Common Pitfalls to Avoid
Do not start at the full maintenance dose (4 mg, 8 mg, or 12 mg) without the initial 2 mg escalation period, as this significantly increases gastrointestinal adverse events including nausea, diarrhea, and vomiting. 1
Be aware that retatrutide causes dose-dependent increases in heart rate that peak at 24 weeks (up to 6.7 beats/min increase), which should be monitored during treatment. 1, 3
The 1 mg dose showed minimal efficacy compared to placebo and is not recommended as a therapeutic dose. 1