Zealand Pharma petrelintide achieves 10.7% weight loss in Phase 2 trial
Zealand Pharma A/S reported positive Phase 2 ZUPREME-1 trial data for petrelintide, showing up to 10.7% weight loss at 42 weeks and improvements in cardiometabolic risk factors. The therapy exhibited placebo-like tolerability with low discontinuation rates. Phase 3 trials are scheduled to begin in the second half of 2026 under a collaboration with Roche.
*this image is generated using AI for illustrative purposes only.
Zealand Pharma A/S announced that petrelintide achieved clinically meaningful, double-digit weight loss in the Phase 2 ZUPREME-1 trial, with data presented at the American Diabetes Association 2026 Scientific Sessions. The 42-week trial demonstrated that once-weekly subcutaneous injections of the amylin analog resulted in mean body weight reductions of up to 10.7% compared to 1.7% for placebo. The treatment was well tolerated, with gastrointestinal adverse events generally similar to placebo and low rates of discontinuation.
The randomized, double-blind, parallel-group, dose-finding trial enrolled 485 adults randomized 5:1 to receive petrelintide or placebo. The trial met its primary endpoint at week 28, showing statistically significant and clinically meaningful reductions in body weight from baseline across all five treatment arms compared to placebo. Secondary and exploratory endpoints assessed at week 42 included changes in body weight, waist circumference, and cardiometabolic risk factors.
Key Efficacy and Safety Findings
Petrelintide treatment led to significant improvements in cardiovascular risk factors. Reductions in waist circumference ranged from 7.9-10.8 cm versus 4.3 cm for placebo. High-sensitivity C-reactive protein (hsCRP) decreased by 17-41% compared to 6% for placebo, while triglycerides fell by 12-21% versus 9% for placebo.
| Metric | Petrelintide Range | Placebo |
|---|---|---|
| Weight Reduction | Up to 10.7% | 1.7% |
| Waist Circumference | 7.9–10.8 cm | 4.3 cm |
| hsCRP Reduction | 17–41% | 6% |
| Triglyceride Reduction | 12–21% | 9% |
Safety data indicated that 88-98% of participants successfully escalated to their targeted maintenance dose. Most gastrointestinal adverse events were mild, with nausea reported in 19.6% of participants on petrelintide versus 6.2% on placebo. Vomiting was rare at 3.0% for petrelintide compared to 6.2% for placebo. Only 1.5% of participants discontinued treatment due to gastrointestinal adverse events, with no unexpected safety findings.
Development Timeline and Collaboration
David Kendall, Chief Medical Officer of Zealand Pharma, highlighted the potential of petrelintide to address challenges of treatment durability and tolerability. The data supports the advancement of the program into Phase 3 trials. In 2025, Zealand Pharma entered an exclusive collaboration and licensing agreement with Roche to co-develop and co-commercialize petrelintide. The companies received formal endorsement to advance the asset into Phase 3 trials in April 2026, with initiation planned for the second half of 2026.
How will the competitive landscape of the obesity market impact petrelintide's market share upon potential launch?
What specific endpoints will be prioritized in the Phase 3 trials to differentiate petrelintide from existing GLP-1 therapies?
How will the collaboration with Roche influence the commercialization strategy and pricing of petrelintide?
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