Zealand Pharma announced positive topline results on October 7, 2026, from its Phase 2 ZUPREME-2 trial of petrelintide in 220 participants with overweight or obesity and type 2 diabetes. The trial met its primary endpoint, with participants achieving up to 9.2% mean weight loss over 28 weeks compared to 2.0% for placebo. Petrelintide also improved glycemic control and demonstrated a favorable tolerability profile. Zealand Pharma and Roche have initiated a Phase 3 program enrolling 7,000 participants.
ZUPREME-2 trial design and overview
- ▪Zealand Pharma announced on October 7, 2026, that its Phase 2 ZUPREME-2 trial of the experimental drug petrelintide met its primary endpoint in people with overweight or obesity and type 2 diabetes.
- ▪The ZUPREME-2 trial enrolled 220 participants in the United States with a mean baseline BMI of 36.3 kg/m² and a mean baseline HbA1c of 8.0%.
- ▪The ZUPREME-2 trial evaluated once-weekly subcutaneous injections of petrelintide or placebo over a 28-week period.
Weight loss efficacy of petrelintide
- ▪The weight loss results across the three petrelintide treatment arms in the ZUPREME-2 trial ranged from 7.4% to 9.2% under the efficacy estimand.
- ▪Participants in the ZUPREME-2 trial achieved up to 9.2% mean weight loss from baseline across three treatment arms, compared to 2.0% with placebo.
Clinical implications
- ▪Zealand Pharma Chief Medical Officer David Kendall stated that the ZUPREME-2 trial results demonstrate petrelintide's promise as a standalone treatment for people with overweight or obesity and type 2 diabetes.
- ▪Zealand Pharma Chief Medical Officer David Kendall stated that the improvements in glycemic control combined with weight reduction are essential for supporting long-term benefits in patients.
Safety and tolerability of petrelintide
- ▪The treatment discontinuation rate due to gastrointestinal adverse events in the ZUPREME-2 trial was 1.9% for petrelintide compared to 1.7% for placebo.
- ▪The most frequently reported adverse events in the ZUPREME-2 trial were gastrointestinal-related, with the majority classified as mild and occurring during the dose escalation period.
- ▪The safety and tolerability profile of petrelintide in the ZUPREME-2 trial was consistent with findings from the 42-week Phase 2 ZUPREME-1 trial.
Phase 3 clinical program plans
- ▪The Phase 3 trials, named ZUPREME-3, ZUPREME-4, and ZUPREME-5, will evaluate petrelintide in people with obesity or overweight without type 2 diabetes, with type 2 diabetes, and with established cardiovascular disease.
- ▪Zealand Pharma and Roche have initiated a Phase 3 program consisting of three trials expected to enroll approximately 7,000 participants in total.
Collaboration between Zealand Pharma and Roche
- ▪Zealand Pharma and Roche plan to initiate a Phase 2 trial in the second half of 2026 evaluating petrelintide in combination with Roche's GLP-1/GIP receptor dual agonist enicepatide.
- ▪Zealand Pharma and Roche entered into an exclusive collaboration and licensing agreement in 2025 to co-develop and co-commercialize petrelintide.
Debatable claims
- ▪Petrelintide's tolerability profile is superior to that of existing GLP-1 obesity treatments
- ▪For diabetic obesity patients, glycemic control matters more than absolute weight loss
- ▪Petrelintide is strong enough to compete with established GLP-1 weight-loss drugs
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