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Phase 2 Escalation Protocol (Jastreboff et al., 2023) The trial employed a 4-week dose escalation to minimize gastrointestinal adverse events: Weeks 1-4: 2 mg subcutaneous once weekly Weeks 5-8: 4 mg once weekly (regardless of target maintenance dose) Weeks 9-12: Escalation to target dose (8 mg or 12 mg groups only) Weeks 13-48: Maintenance at target dose The 4 mg initial step proved critical: direct initiation at 8 mg or 12 mg produced 34% discontinuation rates in pilot cohorts versus 6.7% with gradual escalation

The critical error occurs during the freeze-thaw transition: removing a vial from the freezer, leaving it at room temperature while preparing supplies, then returning it unused

Retatrutide produced 28.7% body weight loss at 68 weeks in Phase 3 trials

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