Dapiglutide

Zealand Pharma's ZP7570, a lipidated GLP-2 analog engineered to activate both GLP-1 and GLP-2 receptors, which lowered body weight in a phase 1b trial, missed its primary endpoint in the phase 2a DREAM trial, and was paused in November 2025.

Also referenced as: ZP7570, ZP-7570

Also appears in: Metabolic

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What is Dapiglutide?

Dapiglutide, developed by Zealand Pharma under the code ZP7570, is a synthetic 33-amino-acid peptide built on the backbone of human GLP-2 and engineered so that it also activates the GLP-1 receptor. Relative to native GLP-2 (His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu-Ala-Ala-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp), the structure registered in PubChem (CID 171934788; molecular formula C192H302N46O57; molecular weight about 4,167 Da) keeps the N-terminal His-Ala and carries nine substitutions: Glu3, Thr7, Ser8, Leu10, Ala11, Gln17, Ala24, His29 and, at position 16, an alpha-methylated lysine whose side chain is acylated through a gamma-glutamyl spacer with an 18-carbon fatty diacid (17-carboxyheptadecanoyl). That fatty-diacid side chain binds albumin, the same protraction strategy used in semaglutide, and gives the molecule a terminal half-life of 123 to 129 hours, about five days. Zealand describes the design as a GLP-2 backbone with substitutions chosen to dial in higher potency at the GLP-1 receptor while retaining GLP-2 receptor activity, and in rodents dapiglutide behaves as a potent agonist at both receptors (Reiner et al., JPEN. Journal of Parenteral and Enteral Nutrition, 2022;46(5):1107–1118). Dapiglutide is both the INN and the USAN.

It matters because Zealand positioned it as a potentially first-in-class unimolecular GLP-1/GLP-2 co-agonist for obesity, pairing the appetite-suppressing, weight-lowering action of GLP-1 (7-37) receptor agonists with the intestinotrophic, barrier-tightening action of GLP-2 that underlies teduglutide, glepaglutide and apraglutide. The hypothesis was that improving gut barrier function would dampen the low-grade systemic inflammation that accompanies obesity and drives its comorbidities. No dapiglutide product is approved anywhere, and Zealand paused development in November 2025, and the phase 2b trial it had planned for 2025 was never registered.

How it works

• GLP-1 receptor agonism lowers food intake and slows gastric emptying. GLP-1 receptor activation in the brainstem and hypothalamus reduces appetite, delays gastric emptying and stimulates glucose-dependent insulin secretion, the mechanism shared by every approved GLP-1-based obesity drug (Drucker, Cell Metabolism, 2018;27(4):740–756). In rodents dapiglutide improved oral glucose tolerance and reduced intestinal transit time (Reiner et al., JPEN. Journal of Parenteral and Enteral Nutrition, 2022;46(5):1107–1118), and in Zealand’s four-week healthy-volunteer trial (NCT04612517) weekly dosing produced dose-dependent reductions in gastric emptying, plasma glucose and insulin.
• GLP-2 receptor agonism drives intestinal growth. GLP-2 induces crypt-cell proliferation and increases small-bowel mass and villus height (Drucker et al., Proceedings of the National Academy of Sciences of the United States of America, 1996;93(15):7911–7916), acting through a receptor expressed on enteroendocrine cells rather than on the absorptive enterocytes themselves (Yusta et al., Gastroenterology, 2000;119(3):744–755). In a mouse model of short bowel with 40% ileocecal resection, dapiglutide increased villus height and intestinal length, promoted body-weight recovery despite unchanged intake of liquid diet, reduced stool water loss and lowered plasma aldosterone (Reiner et al., JPEN. Journal of Parenteral and Enteral Nutrition, 2022;46(5):1107–1118).
• Tightening of the paracellular barrier. In the jejunum of short-bowel mice, dapiglutide increased claudin-7 expression and tightened the tight-junction leak pathway while promoting cation size selectivity through claudin-2 and claudin-10b and preserving claudin-15 along the crypt-villus axis; it produced no barrier effect in the colon (Reiner et al., Annals of the New York Academy of Sciences, 2022;1514(1):132–141). The obesity rationale rests on the earlier observation that GLP-2 signaling improves gut permeability and lowers plasma lipopolysaccharide and inflammatory markers in obese mice (Cani et al., Gut, 2009;58(8):1091–1103).

Research status

Phase 1 in healthy volunteers. The first-in-human single ascending dose trial (NCT03994549) randomized 64 healthy adults between June 14, 2019 and November 2, 2020, and a multiple ascending dose trial (NCT04612517) enrolled 40 healthy adults from October 26, 2020 to August 30, 2021; both were sponsored by Zealand and neither has posted results on the registry. In its September 9, 2024 announcement Zealand summarized the multiple-dose trial as showing dose-dependent weight loss of up to 4.3% from baseline after four weeks of treatment, dose-dependent delays in gastric emptying and reductions in plasma glucose and insulin, a mean half-life of 123 to 129 hours across the four dose cohorts, and tolerability in line with GLP-1 and GLP-2 receptor agonists.

Phase 1b multiple ascending dose trial in overweight and obesity (NCT06000891). A single-center, double-blind, placebo-controlled trial began on September 15, 2023 in participants with a BMI of 27.0 to 39.9 kg/m2 and no lifestyle intervention. Part 1 randomized 54 participants (about 85% male, median age 46, median BMI 30.0 kg/m2) 14:4 to dapiglutide or placebo in three cohorts with target doses of 7.5, 10 and 13 mg for 13 weekly doses, with dose escalation every second week. On September 9, 2024 Zealand reported placebo-adjusted mean weight reductions of up to 8.3% (up to 6.2% loss on dapiglutide against a 2.1% gain on placebo), no severe treatment-emergent adverse events, one serious adverse event judged unrelated to the drug, two discontinuations for moderate vomiting, mild injection-site reactions in a few participants and anti-drug antibodies in 14.3% of participants. Part 2 randomized 30 participants (about 93% male, median age 44.5, median weight 91.9 kg, median BMI 28.8 kg/m2) 2:1 to dapiglutide escalated every fourth week up to 26 mg or placebo for 28 weekly doses. On June 18, 2025 Zealand reported an estimated mean weight change of −11.6% from baseline with dapiglutide against −0.2% with placebo, no severe or serious treatment-emergent adverse events, mostly mild gastrointestinal events led by nausea and vomiting, and two withdrawals for adverse events, one of them gastrointestinal. The registry lists the trial as terminated by sponsor decision after the last participant’s last visit on March 21, 2025, with 84 participants enrolled and no posted results, and neither part has appeared in a peer-reviewed journal.

DREAM phase 2a (NCT05788601). An investigator-initiated, 12-week, double-blind, placebo-controlled trial at Copenhagen University Hospital, Herlev and Gentofte, funded by an unrestricted grant from Zealand, randomized 54 adults with obesity (BMI of 30 kg/m2 or higher; 63% women; mean weight 101.3 kg; mean BMI 35.2 kg/m2) 1:1:1 to once-weekly subcutaneous dapiglutide 4 mg, 6 mg or placebo between April 27, 2023 and April 24, 2024, without a lifestyle intervention; people with HbA1c of 48 mmol/mol or higher or a recent weight change of 5% or more were excluded. The primary endpoint, percentage change in body weight at week 12, was not met: 6 mg dapiglutide produced a placebo-adjusted mean change of −2.1% (95% CI −4.3 to 0.2; p = 0.076). Reduced appetite and nausea were the common adverse events, no participant stopped because of drug-related adverse events, and dropout was 0% on placebo, 11% on 4 mg and 6% on 6 mg. The authors concluded that 4 and 6 mg did not produce a statistically significant weight difference from placebo and that higher doses in larger, longer studies would be needed to evaluate the compound (Nielsen et al., EClinicalMedicine, 2026;93:103801). The registry entry, last updated December 5, 2024, still lists the trial as active, not recruiting, with an estimated completion of August 15, 2025.

Formulation bridging (NCT06758583). An open-label, randomized, parallel-group phase 1 trial in 30 participants with overweight or obesity compared the pharmacokinetics of a single 7.5 mg subcutaneous dose drawn from 10 mg/mL and 25 mg/mL drug-product concentrations; it ran from December 23, 2024 to April 25, 2025 and has no posted results.

Development paused. After the 13-week data Zealand said it planned a phase 2b trial in people with overweight and obesity for the first half of 2025 and intended to evaluate dapiglutide in obesity-related comorbidities. No such trial appears on ClinicalTrials.gov. In its results for the first nine months of 2025, published November 13, 2025, the company stated that development of dapiglutide had been paused as part of active portfolio management, focusing investment on programs it considers to have the greatest potential for clinical differentiation. Zealand’s second quarter 2026 presentation still charts dapiglutide in its obesity pipeline as paused. As of November 2026 the five registered dapiglutide trials are all completed, terminated or closed to enrollment, none is recruiting, and no marketing application has been filed in any jurisdiction.

Common dosage forms

• Investigational subcutaneous solution. Dapiglutide was supplied only to clinical-trial sites as a solution for subcutaneous injection at drug-product concentrations of 10 mg/mL and 25 mg/mL, administered by trial staff.
• No approved presentation. No pen, vial, oral or other dapiglutide product is approved or marketed in any country.

Key considerations

• Regulatory status. The Research Market status reflects the absence of any FDA-approved or foreign-approved dapiglutide product and of any active clinical trial since Zealand Pharma paused development in November 2025. The sponsor describes the program as paused rather than terminated, and no new trial or application had been announced as of November 2026.
• The weight-loss signal rests on unpublished company data. The 8.3% placebo-adjusted reduction at 13 weeks and the 11.6% reduction at 28 weeks come from company announcements of a small, single-center phase 1b trial in a mostly male, relatively lean population with no posted or published results; the only peer-reviewed efficacy trial, DREAM, missed its primary endpoint at 4 and 6 mg.
• The GLP-2 hypothesis is untested in humans. The inflammation and gut-barrier rationale has been demonstrated only in mice; no human trial has reported inflammatory markers, intestinal permeability or comorbidity outcomes with dapiglutide, so whether GLP-2 activity adds anything to GLP-1 agonism in obesity remains unknown.
• Safety record is short. Gastrointestinal adverse events, mostly mild nausea and vomiting, mild injection-site reactions and anti-drug antibodies in 14.3% of participants are the reported signals across five small trials that enrolled 272 participants in total, placebo recipients included, and no exposure beyond 28 weeks exists. GLP-2 receptor agonists such as teduglutide carry a class concern about accelerating growth of intestinal polyps or neoplasia because of their trophic effect, and it has not been examined for dapiglutide.
• Naming. Dapiglutide, ZP7570 and ZP-7570 denote the same lipidated GLP-2-based peptide. It is distinct from Zealand’s selective GLP-2 analog glepaglutide, from the glucagon/GLP-1 dual agonist survodutide and from the amylin analog petrelintide, and it is not an analog of GLP-1 despite activating the GLP-1 receptor.