Dual GLP-1/GLP-2 Agonist Dapiglutide Achieves 11.6% Mean Weight Loss at 28 Weeks in Phase 1b Trial

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Zealand Pharma announced positive topline results from Part 2 of its phase 1b multiple ascending dose (MAD) trial of dapiglutide, a dual GLP-1/GLP-2 receptor agonist under investigation for the treatment of overweight and obesity. After 28 weeks of once-weekly treatment, participants receiving dapiglutide experienced a mean body weight reduction of 11.6%, with no accompanying lifestyle modifications.

The randomized, double-blind, placebo-controlled trial enrolled 30 participants (approximately 93% men) with a median age of 44.5 years, a median baseline weight of 91.9 kg, and a median BMI of 28.8 kg/m². Individuals were randomized in a 2:1 ratio to receive either dapiglutide (escalated to 26 mg) or placebo via subcutaneous injection once weekly. At week 28, participants on dapiglutide showed a mean 11.6% reduction in body weight, compared with 0.2% in the placebo group.

“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 was well tolerated, with no serious or severe treatment-emergent adverse events reported. Most adverse events were mild and gastrointestinal in nature, including nausea and vomiting, consistent with other incretin-based therapies. Two participants discontinued due to adverse events, one related to GI symptoms. Injection site reactions were infrequent and all mild.

Dapiglutide combines GLP-1–mediated appetite suppression with GLP-2 activity aimed at improving intestinal barrier function and addressing obesity-related comorbidities driven by low-grade inflammation. The dual mechanism positions dapiglutide as a potential first-in-class therapy targeting both weight loss and associated inflammatory conditions.

Part 1 of the phase 1b trial, previously reported, showed up to 8.3% placebo-adjusted weight loss after 13 weeks. Detailed data from Part 1 will be presented at the American Diabetes Association’s 85th Scientific Sessions on June 20, 2025.

Dapiglutide continues to advance in Zealand’s obesity pipeline, alongside its amylin analog petrelintide, as the company explores next-generation weight management strategies.

Source: Zealand Pharma announces positive topline results from 28-week Phase 1b trial with GLP-1/GLP-2 receptor dual agonist dapiglutide. News release. Zealand Pharma. June 18, 2025. Accessed June 20, 2025. https://www.globenewswire.com/news-release/2025/06/18/3101731/0/en/Zealand-Pharma-announces-positive-topline-results-from-28-week-Phase-1b-trial-with-GLP-1-GLP-2-receptor-dual-agonist-dapiglutide.html