New data from Phase 2 ZUPREME-1 trial at the American Diabetes Association 2026 Scientific Sessions further support potential of petrelintide to redefine the weight management experience for people living with overweight and obesity
Press release – No. 13 / 2026
New data from Phase 2 ZUPREME-1 trial at the American Diabetes Association 2026 Scientific Sessions further support potential of petrelintide to redefine the weight management experience for people living with overweight and obesity
- Clinically meaningful, double-digit weight loss demonstrated through week 42
- Placebo-like tolerability observed and low rates of treatment discontinuation due to gastrointestinal adverse events
- Treatment associated with improvements in cardiometabolic disease risk factors, including reductions in waist circumference, high-sensitivity C-reactive protein and triglycerides
- Data reinforces the potential of petrelintide to enhance treatment persistence and address current challenges of treatment durability, tolerability and acceptability
- Phase 3 trials for chronic weight management planned for initiation in the second half of 2026
Copenhagen, Denmark, June 5, 2026 – Zealand Pharma A/S (NASDAQ:ZEAL) (CVR-no. 20045078), a biotechnology company transforming the future of metabolic health, today 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® (ADA), 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 (AEs) generally similar to placebo.
Prof. W. Timothy Garvey, MD, Department of Nutrition Sciences, University of Alabama at Birmingham, said, "As we continue to advance the field of obesity medicine, expanding the therapeutic options beyond the current single class of treatments is critical. People living with overweight and obesity need treatments they can stay on long-term, that deliver meaningful weight loss and with a tolerability profile that supports adherence. These data highlight the potential of petrelintide to be just such a treatment – effective and well-tolerated with the potential to facilitate long-term obesity therapy".
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.
Key Findings
- 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).
- 88-98% of participants successfully escalated to their targeted maintenance dose of petrelintide.
- Most (>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 (<7.5%) for petrelintide and placebo.
- Only 1.5% of participants discontinued petrelintide due to gastrointestinal AEs, and there were no unexpected safety findings.
- Petrelintide was associated with meaningful improvements in key cardiovascular risk factors, with the reductions with petrelintide ranging from 7.9-10.8cm for waist circumference (vs 4.3 cm with placebo), 17-41% for high-sensitivity C-reactive protein (hsCRP) (vs 6% with placebo) and 12-21% for triglycerides (vs 9% with placebo).
David Kendall, MD, Chief Medical Officer of Zealand Pharma, said, "With real-world persistence on current therapies disappointingly low, we must address the challenges of treatment durability, tolerability and acceptability if we are to realize the long-term benefits and sustained improvements in health outcomes from the therapeutic management of overweight and obesity. The double-digit weight reduction seen after 42 weeks of petrelintide treatment, along with rates of adverse events generally at or below the rates observed with placebo, highlight the potential of this novel amylin agonist as a future first-choice therapy for chronic weight management."
Dr. Garvey chairs the conference symposium, Amylin as a Novel Diabetes and Obesity Therapy, today, June 5, from 3:45-5:15 PM CT (22.45-00.15 CET) in Great Hall A of the Ernest N. Morial Convention Center. At this symposium, Carel Le Roux, MBChB, MSC, FRCP, FRCPath, PhD and Professor of Experimental Pathology, will present selected data from the ZUPREME-1 trial. Full results from the ZUPREME-1 trial will be published later this year.
The ZUPREME-1 findings will also be presented to the ADA's 2026 Scientific Sessions audience by Prof. W. Timothy Garvey, MD, Department of Nutrition Sciences, University of Alabama at Birmingham, tomorrow, June 6, during a late-breaking session in ePoster Theater A (Halls B1-C) from 1:30-1:40 PM CT (20.30-20.40 CET).
In 2025, Roche and Zealand Pharma entered into an exclusive collaboration and licensing agreement to co-develop and co-commercialize petrelintide for people living with overweight and obesity. In April 2026 the companies announced formal endorsement to advance petrelintide into Phase 3 trials. The initiation is planned for the second half of 2026.
About ZUPREME-1
ZUPREME-1 was a randomized, double-blind, placebo-controlled, parallel-group, multinational, multicenter, dose-finding, Phase 2 clinical trial (ClinicalTrials.gov ID: NCT06662539). The trial compared five doses of once-weekly petrelintide with placebo, when added to a reduced-calorie diet and increased physical activity in people with obesity or overweight with weight-related comorbidities.
The trial included a screening period, a dose escalation period of up to 16 weeks with dose escalation every fourth week, followed by a maintenance period until week 42, and a safety follow-up period after treatment was completed until week 51. ZUPREME-1 enrolled 493 participants across 32 sites in the United States, Poland, and Romania.
The primary endpoint in the trial is the percentage change in body weight from baseline to week 28. Secondary endpoints include, but are not limited to, percentage change in body weight from baseline to week 42, change in waist circumference, change in hemoglobin A1c (HbA1c), change in high-sensitivity C-reactive protein (hsCRP), change in fasting lipids, and change in fasting glucose.
About petrelintide
Petrelintide is a long-acting amylin analog suitable for once-weekly subcutaneous administration that has been designed with chemical and physical stability with no fibrillation around neutral pH, allowing for co-formulation and co-administration with other peptides1. 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 leptin2,3, inducing a sense of feeling full faster.
About Zealand Pharma
Zealand Pharma A/S (NASDAQ:ZEAL) is a biotechnology company focused on advancing medicines for obesity and metabolic health. Combining more than 25 years of peptide R&D expertise with a proprietary data platform that leverages advanced data driven and AI/ML approaches, Zealand Pharma aims to lead a new era in obesity and metabolic health.
To date, more than ten Zealand Pharma invented drug candidates have entered clinical development, of which two products have reached the market and three candidates are in late-stage development. The Company has collaborations with global pharmaceutical and biotechnology partners for research, development, and commercialization.
Founded in 1998, Zealand Pharma is headquartered in Copenhagen, Denmark, with a U.S. presence in Boston, Massachusetts. Learn more at www.zealandpharma.com.
Forward looking statements
This press release contains "forward-looking statements", as that term is defined in the Private Securities Litigation Reform Act of 1995 in the United States, as amended, even though no longer listed in the United States this is used as a definition to provide Zealand Pharma's expectations or forecasts of future events regarding the research, development and commercialization of pharmaceutical products, the timing of the company's pre-clinical and clinical trials and the reporting of data therefrom. These forward-looking statements may be identified by words such as "aim," "anticipate," "believe," "could," "estimate," "expect," "forecast," "goal," "intend," "may," "plan," "possible," "potential," "will," "would" and other words and terms of similar meaning. You should not place undue reliance on these statements, or the scientific data presented. The reader is cautioned not to rely on these forward-looking statements. Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions, which may cause actual results to differ materially from expectations set forth herein and may cause any or all of such forward-looking statements to be incorrect, and which include, but are not limited to, unexpected costs or delays in clinical trials and other development activities due to adverse safety events, patient recruitment or otherwise; unexpected concerns that may arise from additional data, analysis or results obtained during clinical trials; our ability to successfully market both new and existing products; changes in reimbursement rules and governmental laws and related interpretation thereof; government-mandated or market-driven price decreases for our products; introduction of competing products; production problems at third party manufacturers; dependency on third parties, for instance contract research or development organizations; unexpected growth in costs and expenses; our ability to affect the strategic reorganization of our businesses in the manner planned; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies, or may reject, fail to approve or may delay approval of our drug candidates or expansion of product labeling; failure to obtain regulatory approvals in other jurisdictions; exposure to product liability and other claims; interest rate and currency exchange rate fluctuations; unexpected contract breaches or terminations; inflationary pressures on the global economy; and political uncertainty. If any or all of such forward-looking statements prove to be incorrect, our actual results could differ materially and adversely from those anticipated or implied by such statements. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. All such forward-looking statements speak only as of the date of this company announcement and are based on information available to Zealand Pharma as of the date of this announcement. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.
Contacts
Eric Rojas (Investors)
Vice President, Head of Investor Relations
Zealand Pharma
Email: erojas@zealandpharma.com
Neshat Anis Ahmadi (Investors)
Investor Relations Manager
Zealand Pharma
Email: neahmadi@zealandpharma.com
Rachel James-Owens (Media)
Vice President, Corporate Communications & Media Relations
Zealand Pharma
Email: rjamesowens@zealandpharma.com
Andreas Hylleberg Mølleskov (Media)
Director, External Communications
Zealand Pharma
Email: ahylleberg@zealandpharma.com
Amber Fennell, Jessica Hodgson, Sean Leous (Media)
ICR Healthcare
Email: zealandpharma@icrhealthcare.com
+44 (0) 7739 658 783
References
1. Eriksson et al. Presentation at ObesityWeek, November 1–4, 2022, San Diego, CA. Link: https://www.zealandpharma.com/media/0gnfxg4b/zp8396-sema-coformulation-obesityweek-2022.pdf.
2. Mathiesen et al. Eur J Endocrinol 2022;186(6):R93–R111.
3. Roth et al. Proc Natl Acad Sci U S A 2008;105(20):7257–7262
