Zealand Pharma Reports Positive Phase 2 Results For Petrelintide, Showing Significant Weight Loss In Obesity Trial

Zealand Pharma A/S, a biotechnology company focused on advancing treatments for metabolic health, has announced positive topline results from its Phase 2 ZUPREME-1 dose-finding clinical trial evaluating the investigational drug petrelintide for weight management. The study compared once-weekly subcutaneous injections of petrelintide with placebo in 493 adults living with overweight or obesity. Participants in the trial had an average baseline body mass index (BMI) of 37 kg/m², and 53% of the participants were women. The study evaluated the drug’s effects on body weight as well as its safety and tolerability.

The trial successfully met its primary endpoint, demonstrating that petrelintide produced statistically significant and clinically meaningful reductions in body weight compared with placebo after 28 weeks of treatment. The medication was administered once weekly, with doses gradually increased every four weeks. Across all five petrelintide treatment groups, participants experienced significant weight reduction compared with those receiving placebo.

Weight loss benefits continued through week 42 of the trial. Using the efficacy estimand, participants receiving petrelintide achieved an average body weight reduction of up to 10.7% from baseline, compared with a 1.7% reduction in the placebo group. The difference between the two groups was statistically significant, with a p-value of less than 0.001. 

In the treatment group that achieved the highest level of weight reduction, 98% of participants were able to successfully reach the targeted maintenance dose, indicating strong adherence to the dose-escalation schedule and suggesting that the treatment approach was highly tolerable. Body weight reduction calculated using the treatment regimen estimand was largely consistent with the efficacy estimand results. The trial also showed a notable difference between genders, with female participants experiencing greater weight loss on average compared with male participants.

Adam Steensberg, President and Chief Executive Officer of Zealand Pharma, said the results highlight the strong potential of petrelintide in the field of weight management. He explained that the drug’s tolerability profile, which was comparable to placebo, exceeded the company’s expectations and, when combined with the observed double-digit weight reduction, suggests the possibility of a new standard in obesity treatment. He emphasized that long-term success in treating obesity depends on therapies that patients are able and willing to continue using, and he believes these findings bring the company closer to providing treatments that better fit the everyday lives of people living with obesity.

Petrelintide also demonstrated a favorable safety and tolerability profile throughout the study. The rate of treatment discontinuation due to adverse events was 4.8% among participants receiving petrelintide in the most effective treatment arm, compared with 4.9% in the placebo group. The most commonly reported adverse events were related to the gastrointestinal system, but the majority of these were mild. Interestingly, the proportion of participants who experienced vomiting while receiving petrelintide was lower than in the placebo group, and no cases of vomiting were reported in the treatment arm that achieved the greatest weight reduction. 

The occurrence of diarrhea and constipation remained in the single-digit range and was comparable to placebo. Nausea occurred less frequently than in a previous 16-week Phase 1b study of petrelintide, which had used a faster dose escalation schedule of every two weeks. In the current Phase 2 trial, most cases of nausea were mild, and reports of nausea were almost nonexistent after participants reached their target maintenance dose.

No unexpected safety concerns were observed during the trial. Specifically, researchers did not identify new safety signals related to alopecia, fatigue, or neuropsychiatric adverse events such as headache or depression. Injection site reactions were rare and occurred at rates similar to those seen with placebo. Overall withdrawal from the study for any reason was 8.4% among participants receiving petrelintide, compared with 13.6% in the placebo group.

David Kendall, MD, Chief Medical Officer of Zealand Pharma, said the company is encouraged by the Phase 2 findings. He noted that the trial demonstrated both strong weight loss results and an exceptional tolerability profile, with gastrointestinal side effects occurring at rates similar to placebo. According to Dr. Kendall, the results strengthen the possibility that petrelintide could represent a new class of therapy and improve the overall treatment experience for people living with overweight or obesity. The company now plans to move forward with the development program and aims to initiate Phase 3 clinical trials later this year.

The final results of the ZUPREME-1 study, including a nine-week safety follow-up period, are expected to be presented at a scientific conference in 2026. Data from this study will help guide the design and structure of future Phase 3 trials evaluating petrelintide. Zealand Pharma is also conducting additional studies involving the drug. A second Phase 2 trial, known as ZUPREME-2, is currently evaluating petrelintide as a monotherapy in people with overweight or obesity who also have type 2 diabetes. Topline results from this study are expected in the second half of 2026. In addition, a Phase 2 trial investigating a combination therapy of petrelintide and CT-388 is scheduled to begin in the first half of 2026.

The development of petrelintide is also supported through a major industry collaboration. In 2025, Roche and Zealand Pharma entered into an exclusive collaboration and licensing agreement to co-develop and co-commercialize petrelintide as a treatment for people living with overweight and obesity. This partnership is expected to support the continued advancement of the therapy and expand its potential global impact in addressing obesity and related metabolic health challenges.