Zealand Pharma reveals positive top-line results from the ZUPREME-1 Phase 2 trial, where petrelintide, a long-acting amylin analog, achieved up to 10.7% mean body weight reduction at week 42 compared to 1.7% with placebo.4140
Trial Overview
ZUPREME-1 enrolls 493 participants with overweight or obesity (mean BMI 37 kg/m², 53% female) across 33 sites in the US, Poland, and Romania. The randomized, double-blind, placebo-controlled study tests five escalating doses of once-weekly subcutaneous petrelintide alongside diet and exercise. Primary endpoint measures percent body weight change from baseline to week 28, with secondary endpoints including week 42 weight loss, waist circumference, HbA1c, hsCRP, lipids, glucose, and body composition via MRI.41
Efficacy Highlights
All petrelintide arms deliver statistically significant weight loss versus placebo at week 28, sustained to week 42. The highest dose yields 10.7% reduction (efficacy estimand, p<0.001), with 98% of participants reaching maintenance dose. Females experience greater loss than males. Results remain consistent under treatment regimen estimand.40
Safety and Tolerability
Petrelintide shows placebo-comparable profile. Adverse event discontinuations hit 4.8% in top dose arm versus 4.9% placebo. Overall withdrawals stand at 8.4% versus 13.6%. Mild GI events dominate; vomiting rates fall below placebo (none in top arm), nausea drops post-escalation, diarrhea/constipation stay single-digit. No signals in alopecia, fatigue, neuropsychiatric issues, or injection reactions.39
Executive Insights
“Petrelintide has the potential to redefine weight management,” states Adam Steensberg, President and CEO. “Its placebo-like tolerability exceeds our expectations and, combined with double-digit weight reduction, sets a new standard.”41
David Kendall, MD, Chief Medical Officer, adds: “These data reinforce petrelintide’s potential to establish a new class of therapy and redefine the weight management experience.”39
Next Steps and Partnership
Findings guide Phase 3 designs, slated for late 2026 start. Full data, including nine-week follow-up, appear at a 2026 congress. ZUPREME-2 topline data in H2 2026 tests petrelintide in type 2 diabetes patients; combo trial with CT-388 launches H1 2026. Roche co-develops and co-commercializes petrelintide globally.38
