Glepaglutide is an investigational long-acting GLP-2 analogue for short bowel syndrome with intestinal failure. A positive phase 3 trial has been published, but the compound is not an approved medicine.

Potential. Review the research and limitations before relying on this record.

Like teduglutide, glepaglutide activates the GLP-2 receptor to promote intestinal mucosal growth and absorptive function. Sequence substitutions make it resistant to rapid DPP-4 degradation. Its prolonged clinical profile is driven largely by slow release of two active metabolites from the subcutaneous depot rather than persistence of unchanged parent peptide.

In 45 healthy volunteers, the two principal active metabolites accounted for more than 98% of steady-state exposure after subcutaneous administration. Estimated effective half-life was 124 hours in one group and 88 hours in another, supporting once- or twice-weekly study schedules. The broad confidence intervals show that these are not precise universal values.

In a 106-participant phase 3 randomised placebo-controlled trial in short bowel syndrome with intestinal failure, the twice-weekly study arm reduced weekly parenteral-support volume more than placebo over 24 weeks and improved response and support-day endpoints. The once-weekly arm did not significantly beat placebo on the primary endpoint. Positive phase 3 publication is substantial evidence, but regulatory approval has not been established.

The phase 3 publication described treatment as generally well tolerated, but the dataset remains far smaller and shorter than post-approval experience with teduglutide. The GLP-2 growth mechanism raises the same unresolved class concerns around accelerating gastrointestinal neoplasia, obstruction, fluid overload, and biliary or pancreatic disease; whether monitoring requirements will match teduglutide can only be set by a regulator. No regulator has approved this substance for the use described here, so there is no label-verified dose, purity standard, or safety monitoring requirement behind it.

This is a source-backed summary, not a recommendation. Read the mechanism, pharmacokinetic, human-evidence and reported-effect fields separately: a mechanism is not an outcome. Availability, legal status and product quality differ by jurisdiction; consult a qualified clinician.