Glucagon-like peptide 2 (GLP-2) is an enterotrophic hormone consisting of 33 amino acids. It derives from a glucagon pro-peptide encoded by the GCG gene, like GLP1 and glucagon itself. GLP-2 exists in enteroendocrine L cells in the intestinal epithelium, and also exists in various neurons in the central nervous system. And it has important regulatory effects in humans and rodents. GLP-2 increases intestinal growth by enhancing crypt cell proliferation and inhibiting apoptosis, which leads to a high degree of villi enlargement and enhanced barrier function. Also, it regulates energy absorption by affecting nutrient intake, nutrient absorption, and mucosal permeability. Importantly, GLP-2 also prevents intestinal dysplasia caused by total parenteral nutrition. GLP-2 receptor (GLP-2R) belongs to the G protein-coupled receptor superfamily and is closely related to the glucagon receptor and GLP1 receptor. Therefore, GLP-2R has become an important target for research on GLP-2-related diseases.

Glepaglutide (ZP1848) is a potent GLP-2R agonist.

Glepaglutide has been reported to enhance intestinal repair and reduce inflammation. The agonist (200 and 400 nmol/kg, s.c., twice a day for 14 days) shows an increase in plasma citrulline concentration and small intestinal mass. Also, it results in a decrease of small intestinal concentrations of the inflammatory marker (AGP and MPO) in rats with small intestinal inflammation. Besides, Glepaglutide (0.1-10 mg/kg, s.c., once daily for 7 days or 26 weeks) results in a dose-dependent increase in small intestine length and weight as well as visually visible thickening and villous hypertrophy in all parts of the small intestine. And it has a long-lasting enterotrophic effect in Wistar rats. Meanwhile, Glepaglutide has therapeutic potential in reducing fecal excretion and increasing intestinal absorption in patients with short bowel syndrome and for Crohn’s disease in clinical trials.

In conclusion, Glepaglutide (ZP1848) is a potent GLP-2R agonist, good for inflammatory bowel disease (IBD) and Crohn’s disease.


[1] Melanie A Markovic, et al. Sci Rep. 2019 Sep 10;9(1):13010. 
[2] Jolanta Skarbaliene, et al. Gastroenterology, 2011, 140(5): S519.
[3] Glerup P, et al. Physiol Res. 2022 Apr 30;71(2):323-326.