Dapiglutide: the peptide acting on two gut receptors

It is a 33-amino-acid peptide with a fatty side chain (C18) that extends its action to about five days, so one injection a week, subcutaneous, is enough. It is built on the backbone of the hormone GLP-2, with changes that add GLP-1 activity. According to the Phase 2 paper, it is about three times more selective for the GLP-1 receptor than for GLP-2.

GLP-2 is associated with growth and function of the gut lining. That is why the compound was first studied for short bowel syndrome and for gut-barrier function.

On 13 Nov 2025 Zealand announced that development "has been paused as part of active portfolio management", to focus investment on programmes with the greatest potential for clinical differentiation. The 2025 annual report lists it as "paused (Phase 2 – ready)". In the text of the 2026 interim reports we checked (first quarter and first half) we did not find it, while other compounds of the company do appear. We found no sign of a restart.

• NCT03994549: Focus: First in human, single doses, healthy · Participants: 64 · Status: Completed 2020
• NCT04612517: Focus: Repeated doses, healthy, 4 weeks · Participants: 40 · Status: Completed 2021
• DREAM (NCT05788601): Focus: Obesity, 12 weeks · Participants: 54 · Status: Completed, published
• NCT06000891: Focus: Obesity, Phase 1b, up to 28 weeks · Participants: 84 · Status: Terminated, reason not stated
• NCT06758583: Focus: Pharmacokinetics, two formulations · Participants: 30 · Status: Completed

DREAM, 12 weeks — peer-reviewed (EClinicalMedicine 2026, PMID 41768273). The study was investigator-initiated at Gentofte Hospital, with an unrestricted grant from Zealand. Among 54 participants (63% women, mean BMI 35.2, no lifestyle intervention):

• At 6 mg the weight difference from placebo was −2.1% (95% confidence interval −4.3 to +0.2, p = 0.076), which is not statistically significant.
• Mean within-group weight change was −2.2% on placebo, −2.9% at 4 mg and −4.3% at 6 mg.
• Weight loss greater than 5% occurred in 8 of 17 at 6 mg (47%) and 4 of 18 on placebo (22%), in a very small sample. No one exceeded 10%.
• Glycated haemoglobin fell slightly (−1.9 and −2.4 mmol/mol, versus −0.1). Participants did not have diabetes, so this is a change in values, not an indication of a therapeutic effect.
• No effect was seen on body composition, blood pressure, liver fat, lipids or quality of life.

The results do not report markers of inflammation or gut permeability. The paper itself notes that human evidence for anti-inflammatory and gut-barrier effects is "less consistent".

Phase 1b — company announcements, not peer-reviewed.

• 13 weeks, 54 participants: weight reduction of up to 8.3% beyond placebo in the dose cohort with the largest result; the other two had a smaller one. Almost all were men (about 85%).
• 28 weeks, 30 participants, doses up to 26 mg: an 11.6% reduction from baseline, versus 0.2% on placebo. The company itself describes the population as "almost entirely male and relatively lean". The company reports no severe or serious adverse events.

Healthy volunteers, 4 weeks — company announcement (poster, 2022), repeated in the DREAM paper: weight reduction of up to 4.3% in 40 people, mostly men with a mean BMI of 24.6.

Clinical-trial facts, not usage instructions. Dapiglutide is an investigational compound without approval. All doses are subcutaneous, once weekly.

• Repeated doses, healthy volunteers (4 weeks): 1.0, 2.25 and 3.5 mg, and one group with 3.5 then 6.0 mg.
• DREAM: start at 2 mg, rising by 2 mg every three weeks to the final dose of 4 or 6 mg.
• Phase 1b, part 1 (company announcements): target doses of 7.5, 10 and 13 mg, rising every second week. The 13 mg group stayed on the target dose for 5 weeks.
• Phase 1b, part 2: up to 26 mg, rising every fourth week. This is the highest dose with data, and it comes from a company announcement.
• Pharmacokinetic study: a single dose of 7.5 mg.

The company reports a mean half-life of 123 to 129 hours in the healthy-volunteer studies and about 120 hours (5 days) in Phase 1b. Peak concentration was reached at 24 hours. The DREAM paper says "approximately five days".

In DREAM, pooled across the 36 who received the drug versus 18 on placebo:

• Reduced appetite: Drug: 61% · Placebo: 33%
• Nausea: Drug: 56% · Placebo: 38%
• Diarrhoea: Drug: 31% · Placebo: 17%
• Constipation: Drug: 31% · Placebo: 11%
• Vomiting: Drug: 11% · Placebo: 11%

There were no drug-related discontinuations. One death occurred in the 6 mg group, from small-cell lung cancer, judged unrelated to treatment.

DREAM excluded people with a history of pancreatitis, a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia, inflammatory bowel disease, a history of colon cancer or polyps, intestinal stenosis, and diabetes.

• The gut barrier and short bowel syndrome. These were studied in mice (JPEN 2022, PMID 34705281); we found no human study.
• Its effect on inflammation and the gut barrier in humans. The markers were registered as secondary endpoints in DREAM but are not reported in the paper.
• Why trial NCT06000891 was terminated.
• The reason for the pause, beyond the company's wording.
• Detailed Phase 1b data, which exist only as announcements.

This content is educational and research-oriented. Dapiglutide is an investigational compound, is not approved as a medicine, and is not intended for human use. This is not medical advice.