Zealand Pharma A/S announced the presentation of additional data from its Phase 2 ZUPREME-1 trial, evaluating investigational petrelintide, at the 2026 Scientific Sessions of the American Diabetes Association, taking place in New Orleans, Louisiana. Results from the 42-week, Phase 2 trial show that participants who received once-weekly subcutaneous injections of petrelintide, an amylin analog, achieved clinically meaningful reductions in body weight compared to placebo. Treatment with petrelintide was associated with improvements in cardiometabolic disease risk factors and was well tolerated with rates of gastrointestinal (GI)-related adverse events generally similar to placebo.

In the double-blind, parallel-group, dose-finding ZUPREME-1 trial, 485 adults (53% female; mean age: 47 years, BMI: 36.7 kg/m2; body weight: 107.1 kg) were randomized (5:1) to weekly subcutaneous injections of five doses of petrelintide or placebo. The trial met its primary endpoint, demonstrating that once-weekly subcutaneous injections of petrelintide resulted in statistically significant and clinically meaningful reductions in body weight from baseline after 28 weeks in all five treatment arms compared to placebo. The trial?s primary endpoint of percentage change in body weight from baseline was measured at Week 28.

Secondary/exploratory endpoints included change in body weight, waist circumference and cardiometabolic risk factors, measured at Week 42, and treatment emergent adverse events. Petrelintide led to mean reductions in body weight from baseline to Week 42 of up to 10.7% vs 1.7% for placebo (efficacy estimand; p<0.001 for all doses vs placebo). Placebo-like tolerability was observed and low rates of treatment discontinuation due to gastrointestinal adverse events.

Treatment was associated with improvements in cardiometabolic disease risk factors, including reductions in waist circumference, high-sensitivity C-reactive protein and triglycerides. The majority (>75%) GI AEs were mild. Nausea was the most common GI AE, reported for 19.6% of participants on petrelintide vs 6.2% on placebo.

Vomiting was rare with petrelintide (3.0% vs 6.2% for placebo), while the rates of diarrhea and constipation were similarly low (1. Human amylin is produced in the pancreatic beta cells and co-secreted with insulin in response to ingested nutrients. Amylin receptor activation has been shown to reduce body weight by restoring sensitivity to the satiety hormone leptin, inducing a sense of feeling full faster. Phase 3 trials for chronic weight management are planned for initiation in the second half of 2026.