GLP-2 analog · short bowel syndrome
Glepaglutide is a lab-made, long-acting version of GLP-2, a gut hormone that helps the intestinal lining grow and absorb nutrients. Zealand Pharma is developing it for adults with short bowel syndrome, where too little working intestine remains after surgery or disease and people rely on intravenous nutrition and fluids.
Natural GLP-2 is a 33-amino-acid gut hormone, but it is chemically unstable and short-lived, which makes it impractical as a medicine3. Glepaglutide swaps several amino acids for stability and adds a tail of six lysines to the end of the chain3. According to the EMA, it acts like GLP-2: it increases blood flow to the intestine, slows gut movement and stomach-acid secretion, and promotes growth of the intestinal lining, with thicker mucosa and deeper crypts6. Injected under the skin, it forms a depot that slowly releases two active metabolites; in healthy volunteers these made up nearly all of the exposure, and the effective half-life was roughly 88 to 124 hours4. The goal is a more absorptive gut, so less fluid and nutrition has to be given by vein.
The key human evidence is the phase 3 EASE SBS 1 trial, which randomized 106 adults with short bowel syndrome and intestinal failure to one of two glepaglutide regimens or placebo for 24 weeks1. The more frequent regimen cut weekly parenteral-support volume significantly more than placebo, more people reached a reduction of at least 20% (66% versus 39%), and five patients (14%) stopped parenteral support entirely, against none on placebo. The less frequent regimen did not separate from placebo on the main endpoints.
A small open-label study in 10 patients, using metabolic balance measurements, found higher energy absorption at 24 weeks and lower parenteral volumes at 52 weeks2. Both studies involved the developer, Zealand Pharma. A second placebo-controlled phase 3 trial, with a long-term open-label phase, began recruiting in 20265.
Not approved by the FDA. In September 2026 the EMA's CHMP recommended EU authorisation, as Zeydovio, for adults with short bowel syndrome; a European Commission decision was still pending at the time of writing6.
The most common side effects listed in the EMA summary are injection-site reactions, stoma complications in people with a stoma, abdominal pain and distension, nausea, vomiting, and fluid retention or overload6. In the 24-week phase 3 trial the drug was reported as generally well tolerated1. Because GLP-2 drives growth of the intestinal lining, longer-term data are still being collected in ongoing trials5.
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