COPENHAGEN, Denmark, June 5, 2026
Zealand Pharma announced new results from its Phase 2 ZUPREME-1 clinical trial evaluating petrelintide, an investigational long-acting amylin analog for chronic weight management, at the American Diabetes Association (ADA) 2026 Scientific Sessions in New Orleans. The findings demonstrated clinically meaningful double-digit weight loss, placebo-like tolerability, and significant improvements in cardiometabolic risk factors, further supporting petrelintide’s potential as a next-generation therapy for people living with overweight and obesity.
Petrelintide Delivers Significant Weight Loss Through 42 Weeks
The randomized, double-blind, placebo-controlled Phase 2 study enrolled 485 adults with obesity or overweight and weight-related comorbidities who received once-weekly subcutaneous injections of petrelintide or placebo. The trial met its primary endpoint at Week 28, demonstrating statistically significant reductions in body weight across all treatment groups. Extended results through Week 42 showed that participants treated with petrelintide achieved mean weight reductions of up to 10.7% from baseline, compared with 1.7% for placebo. Importantly, between 88% and 98% of participants successfully reached their targeted maintenance dose, highlighting strong treatment adherence and dose escalation success.
Favorable Tolerability and Cardiometabolic Benefits
Beyond weight reduction, petrelintide demonstrated a favorable safety and tolerability profile. Gastrointestinal adverse events were generally comparable to placebo, with most events classified as mild in severity. Nausea was the most frequently reported gastrointestinal event, occurring in 19.6% of petrelintide-treated participants compared with 6.2% receiving placebo. Vomiting remained uncommon, affecting only 3.0% of patients receiving petrelintide. Notably, only 1.5% of participants discontinued treatment due to gastrointestinal adverse events, a rate significantly lower than many currently available obesity therapies. In addition to weight loss, petrelintide was associated with meaningful improvements in several cardiometabolic risk markers, including reductions in waist circumference, high-sensitivity C-reactive protein (hsCRP), and triglyceride levels, suggesting broader metabolic health benefits beyond body weight reduction.
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Potential to Improve Long-Term Obesity Treatment Persistence
Investigators emphasized that long-term treatment persistence remains a major challenge in obesity management, with many currently available therapies experiencing high discontinuation rates due to tolerability concerns. The ZUPREME-1 data indicate that petrelintide may help address these challenges by combining clinically meaningful efficacy with placebo-like tolerability. Researchers highlighted the drug’s potential to become a preferred long-term obesity treatment option capable of supporting sustained patient adherence. Petrelintide is designed as a once-weekly amylin receptor agonist that restores sensitivity to satiety signaling and promotes earlier feelings of fullness, offering a mechanism distinct from currently marketed GLP-1-based therapies.
Phase 3 Development Planned for Second Half of 2026
The positive Phase 2 findings further strengthen the development program established through the collaboration between Zealand Pharma and Roche, which entered into an exclusive co-development and co-commercialization agreement for petrelintide in 2025. Following formal endorsement earlier this year, the companies plan to initiate Phase 3 clinical trials in the second half of 2026. Zealand Pharma believes the combination of robust efficacy, favorable tolerability, and improvements in cardiometabolic risk factors positions petrelintide as a promising future therapy for chronic weight management and metabolic health.
Source: Zealand Pharma press release
