TRIUMPH-1 Safety Profile: 4.1% / 6.9% / 11.3% Discontinuation on 4 / 9 / 12 mg Retatrutide vs 4.9% Placebo; Transient ALT Elevations Normalize by Week 24
TRIUMPH-1's safety profile landed alongside the efficacy headline. Discontinuation rates due to adverse events were 4.1%, 6.9%, and 11.3% on retatrutide 4 mg, 9 mg, and 12 mg respectively, versus 4.9% on placebo. The most common adverse events were nausea, diarrhea, constipation, and vomiting — generally mild-to-moderate, concentrated during dose escalation, and decreasing over time. The hepatic-enzyme signal that appeared in TRIUMPH-4 (December 2025) reappeared as transient ALT elevations in a subset of participants on 9 mg and 12 mg dosing, normalizing by week 24. Liver fat dropped >80% on 8-12 mg dosing, supporting the interpretation that the transient transaminitis reflects hepatic triglyceride mobilization rather than hepatotoxicity. The 12 mg discontinuation rate at 11.3% sits modestly above tirzepatide 15 mg in SURMOUNT-1 (~7%) and Wegovy 2.4 mg in STEP 1 (~6.5%) — a tolerability gap that prescribers and patients will weigh against the efficacy gain.