Roche presented ZUPREME-1 Phase 2 data for petrelintide, the once-weekly long-acting amylin analog licensed from Zealand Pharma, at the Monday June 8 investor event. The pitch hinges on tolerability: published topline showed up to 10.7% weight loss at 42 weeks versus 1.7% placebo, with discontinuation 4.8% vs 4.9% placebo and no vomiting at the maximally effective dose. Medical Daily framed the readout as a non-incretin option for the estimated 30-40% of patients who quit GLP-1s for GI side effects. Petrelintide advances to Phase 3 alongside enicepatide.
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.