Overview
Body weight reductions of a mean of 11.6% after 28 weeks with dapiglutide escalated up to 26 mg, with 95% of trial participants being male, a median baseline BMI of 28.5 kg/m2, and no lifestyle modifications
Treatment with dapiglutide was assessed to be safe and well-tolerated with gastrointestinal adverse events consistent with the profile reported with other incretin-based therapies.
Zealand Pharma’s Dapiglutide Shows Promise in Obesity Treatment
Unique, dual mechanism, including GLP-2 activity, designed to target obesity-related comorbid conditions driven by low-grade inflammationZealand Pharma A/S (Nasdaq: ZEAL) (CVR-no. 20045078), a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announces positive topline clinical results from Part 2 of a Phase 1b multiple ascending dose (MAD) trial, investigating safety, tolerability, and clinical effects of 28 weeks of treatment with dapiglutide, a long-acting GLP-1/GLP-2 receptor dual agonist.
Comments from Zealand Pharma
- We are very encouraged by the impressive weight loss with dapiglutide after 28 weeks that appears on par with the most efficacious once-weekly GLP-1 receptor agonist-based therapy on the market today, despite the almost entirely male and relatively lean trial population,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma.
- Dapiglutide is a unique GLP-1 receptor agonist-based therapy, aiming to leverage a dual mechanism that includes GLP-2. Our mid- to late-stage obesity pipeline includes differentiated GLP-1 receptor agonist-based therapies that target people with obesity-related comorbid conditions, and our amylin analog, petrelintide, with potential as a foundational therapy for weight management, addressing unmet needs among the majority of people with overweight and obesity.”
Dapiglutide Phase 1b Trial (Part 2): Key Findings at a Glance
- In this Part 2 of the Phase 1b MAD trial, a total of 30 participants (~93% male) with a median age of 44.5 years, a median baseline body weight of 91.9 kg, and a median baseline BMI of 28.8 kg/m2 were randomized to receive 28 weekly doses of either dapiglutide or placebo (2:1) within one dose cohort.
- At week 28, the estimated mean body weight decreased by 11.6% from baseline among participants on dapiglutide treatment.
- Placebo treatment resulted in a mean body weight decrease of 0.2% from baseline.
- No lifestyle modifications, such as diet or exercise, were included in the trial.
Dapiglutide: Safety and Tolerability at Higher Doses (Phase 1b, Part 2)
- Higher doses of dapiglutide compared to the prior 13-week Part 1 of the trial were assessed to be safe and well-tolerated in the trial, with no severe or serious treatment-emergent adverse events (TEAEs) reported.
- The vast majority of TEAEs were mild and the most common were gastrointestinal (GI), including nausea and vomiting.
- Two participants withdrew due to TEAEs, one of which was related to GI events.
- Overall, the number of GI events observed was consistent with clinical trials of other incretin-based therapies.
- A low number of participants reported injection site reactions, all of which were mild.
About the Phase 1b trial
- The Phase 1b trial is a single-center, randomized, double-blind, placebo-controlled clinical trial in participants with overweight or obesity (eligible BMI 27.0 to 39.9 kg/m2), investigating safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of dapiglutide as subcutaneous injections using a dose escalation scheme (NCT06000891).
- No lifestyle modifications, such as diet or exercise, are included in the trial.
- The trial consists of Part 1 and Part 2.
Part 1
- Part 1 included 54 participants in three cohorts receiving 13 once-weekly doses of dapiglutide or placebo, with rapid dose escalation every second week.
- Participants randomized to the highest dose cohort (13 mg) received the target dose for a period of 5 weeks.
- Topline results from Part 1 showed placebo-adjusted reductions in body weight of up to a mean of 8.3% with dapiglutide after 13 weeks (up to 6.2% mean weight loss on dapiglutide; 2.1% mean weight gain on placebo).
- Detailed results from Part 1 of the Phase 1b MAD trial with dapiglutide will be presented at the American Diabetes Association’s 85th Scientific Sessions in Chicago, Illinois on June 20, 2025.
Part 2
Part 2 of the trial includes 30 participants receiving 28 once-weekly doses of dapiglutide up to 26 mg or placebo within one dose cohort, with dose escalation every fourth week.
About dapiglutide
- Dapiglutide is a long-acting, dual GLP-1/GLP-2 receptor agonist for the potential treatment of obesity-related comorbidities driven by low-grade inflammation.
- This is a potentially first-in-class peptide designed to leverage the weight loss effects of a potent GLP-1 receptor agonist and address comorbidities associated with low-grade inflammation through improved intestinal barrier function by GLP-2 receptor activation.
About low-grade inflammation and obesity
- Excess fat storage associated with obesity can trigger low-grade systemic inflammation through reduced intestinal barrier integrity, or “leaky gut”.
- Obesity-related low-grade inflammation may result in several comorbidities, including cardiovascular disease, liver disease, inflammatory bowel disease, and neuroinflammation.
About Zealand Pharma A/S
- Zealand Pharma A/S (Nasdaq: ZEAL) (""Zealand"") is a biotechnology company focused on the discovery and development of peptide-based medicines.
- More than 10 drug candidates invented by Zealand have advanced into clinical development, of which two have reached the market and three candidates are in late-stage development.
- The company has development partnerships with a number of pharmaceutical companies as well as commercial partnerships for its marketed products.
- Zealand was founded in 1998 and is headquartered in Copenhagen, Denmark, with a presence in the United States.
- For more information about Zealand’s business and activities, please visit www.zealandpharma.com.
Forward looking statements
- This announcement includes “forward-looking statements” as defined by the Private Securities Litigation Reform Act of 1995 in the U.S., used here for clarity despite the company no longer being U.S.-listed.
- These statements reflect Zealand Pharma’s expectations about future events, including:
- Research, development, and commercialization of pharmaceutical products.
- Timing and outcomes of pre-clinical and clinical trials.
- Regulatory submissions and data reporting.
- Forward-looking statements may be identified by terms like “aim,” “anticipate,” “expect,” “plan,” “will,” “may,” and similar expressions.
- Readers are cautioned not to place undue reliance on these statements or the scientific data presented.
- Risks and uncertainties that could cause actual results to differ include:
- Clinical trial delays or safety issues
- Marketing and commercialization challenges
- Regulatory changes or rejections
- Intellectual property disputes
- Manufacturing or supply chain issues
- Economic, political, or geopolitical instability
- Currency fluctuations and inflationary pressures
- Zealand Pharma does not commit to updating these statements after the date of the announcement.
- Information provided is not intended as advertising or medical advice.
