Dapiglutide
Dapiglutide, GLP-1 and GLP-2 receptor dual agonist
Written by Aaron CuhaReviewed Sep 2026
Also known as: ZP7570
The only GLP-1 and GLP-2 dual agonist in obesity, and its proof-of-concept trial missed. Weight change against placebo was 2.1 percent at p equals 0.076 in 54 people over 12 weeks.
Overview
This is a genuinely novel mechanism and a negative result, which is the combination this site exists to publish properly.
Every other dual agonist here pairs GLP-1 with GIP, glucagon or amylin. Dapiglutide pairs it with GLP-2, whose job is the gut lining rather than appetite or glucose. The rationale is that GLP-2 improves intestinal barrier function and reduces inflammation, so a drug hitting both receptors might produce weight loss plus a gut-derived anti-inflammatory benefit.
The 12-week proof-of-concept trial in 54 adults with obesity did not show the weight effect. The 6 mg dose produced a mean bodyweight change of minus 2.1 percent against placebo, with a confidence interval from minus 4.3 to plus 0.2 and p equals 0.076. The investigators' own interpretation is that it did not result in a statistically significant difference, and that higher doses in larger and longer studies are worth testing.
Mechanism of action
A co-agonist at the GLP-1 and GLP-2 receptors from Zealand Pharma. GLP-1 receptor agonism reduces food intake. GLP-2 receptor agonism acts on the intestinal epithelium, increasing mucosal growth and barrier integrity, which is the mechanism behind teduglutide's approval for short bowel syndrome. The hypothesis behind pairing them is that a leaky, inflamed gut contributes to metabolic disease, so repairing the barrier while suppressing appetite might do more than suppressing appetite alone. That hypothesis has not been tested against a clinical inflammatory endpoint.
Human evidence
One 12-week randomised placebo-controlled proof-of-concept trial in 54 people, which missed its primary endpoint. That is the entire human record. The GLP-2 rationale rests on mouse work.
- 54 adults with obesity, three arms, 12 weeks, no concurrent lifestyle intervention, which is an unusually clean design for isolating a drug effect.
- Primary endpoint missed: minus 2.1 percent bodyweight against placebo at the 6 mg dose, 95% CI minus 4.3 to plus 0.2, p = 0.076.
- Safety was good. No participant discontinued because of a drug-induced adverse event, and dropout was low across all arms.
- Reduced appetite and nausea were the common adverse events, confirming the GLP-1 half is doing something.
- The authors support investigating higher doses in larger and longer studies rather than treating the mechanism as dead.
What this does not tell you: 54 people over 12 weeks at doses the investigators themselves consider possibly too low. A confidence interval running from minus 4.3 to plus 0.2 percent does not exclude a useful effect, so this is an inconclusive trial rather than a demonstration that the drug does nothing. Critically, the GLP-2 half of the rationale, gut barrier function and inflammation, was not tested against a clinical endpoint at all, so the interesting part of the hypothesis remains unexamined in people.
Reading the research record
Dapiglutide is worth a page precisely because it did not work yet. The mechanism is the only one of its kind in obesity development, and the trial that tested it is small, short and inconclusive rather than decisive. Both of those facts get lost in the usual coverage, which either ignores a missed endpoint or reports it as a failure.
The honest reading is narrower. A 12-week trial in 54 people at 4 and 6 mg produced a point estimate of 2.1 percent weight loss with a confidence interval crossing zero. That is what an underpowered early trial looks like when a modest effect may exist, and it is also what a trial looks like when nothing is there. The gut barrier claim, which is the actual novelty, has not been measured in a clinical endpoint in humans at all.
The evidence, charted
Fig. 1 · evidence composition
2of 3 citations (67%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Citations here span just two years, 2022 and 2026.
Too few distinct publication years on this page to plot as a timeline.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Approved
CA
Not approved
Approved in 2 of 4, prescription route in 0, not approved in 2. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Human2026
Dapiglutide, a dual GLP-1 and GLP-2 receptor agonist, for obesity: a randomised, double-blind, placebo-controlled parallel-group, proof-of-concept trial
54 adults with obesity in Denmark, 63 percent women, mean bodyweight 101.3 kg and BMI 35.2, randomised 1:1:1 to dapiglutide 4 mg, 6 mg or placebo weekly for 12 weeks with no concurrent lifestyle intervention. Primary endpoint percentage bodyweight change. The 6 mg dose produced a mean change of minus 2.1 percent against placebo (95% CI minus 4.3 to 0.2, p = 0.076), not statistically significant. Safe and well tolerated, with reduced appetite and nausea the common adverse events and no discontinuations for drug-induced adverse events. Dropout 0 percent on placebo, 11 percent on 4 mg and 6 percent on 6 mg. Funded by an unrestricted grant from Zealand Pharma.
EClinicalMedicine - Human2026
A trial of dapiglutide in participants with obesity (DREAM)
The registry record for the trial above.
ClinicalTrials.gov - Animal2022
Dapiglutide, a novel dual GLP-1 and GLP-2 receptor agonist, attenuates intestinal insufficiency in a murine model of short bowel
Mouse. The origin of the GLP-2 half of the rationale, in a short bowel model where intestinal insufficiency was attenuated. This is the intestinal claim in its only tested form, and it was tested in mice with surgically shortened bowels rather than in people with obesity.
Journal of Parenteral and Enteral Nutrition
Frequently asked questions
Did dapiglutide work for weight loss?
Not in its proof-of-concept trial. The 6 mg dose produced 2.1 percent more weight loss than placebo over 12 weeks in 54 people, with a p value of 0.076 and a confidence interval that crossed zero. The investigators call it not statistically significant and recommend testing higher doses.
What does adding GLP-2 do?
In principle it repairs and thickens the intestinal lining and reduces gut inflammation, which is why its analogue teduglutide is approved for short bowel syndrome. Whether that produces any metabolic benefit in obesity is the interesting question, and this trial did not measure a clinical inflammatory or barrier endpoint, so it remains untested in people.
Is the mechanism dead?
No, and it would be wrong to say so from this trial. 54 people, 12 weeks, and doses the sponsors and investigators both consider potentially subtherapeutic. What can be said is that no positive weight loss result exists for it yet.