GLP-2 Agonists

Indications

Teduglutide is indicated in patients with short bowel syndrome who are stable following a period of intestinal adaptation after surgery. Short bowel syndrome is generally defined when there is less than 200cm of small intestine remaining. Patients should be stable on their current parenteral support, and aim to achieve at least a 20% or 1-day reduction in parenteral support after 12 months. The usual dose of teduglutide is 0.05mg/kg once daily and is administered by subcutaneous injection. 

Mechanism of action

GLP-2 is a peptide secreted by the L cells of the intestine and has the following effects:

• Increases intestinal and portal blood flow
• Inhibits gastric acid secretion
• Decreases intestinal motility 

GLP-2 Agonists mimic the action of GLP-2 by binding to GLP-2 receptors, which are mainly located in the gut and the brain. Teduglutide is a GLP-2 Agonist with a single amino acid substitution, leading to a reduction in degradation by the enzyme dipeptidyl peptidase-4 and consequently an extended half life. 

Teduglutide has been found to increase bowel surface area by lengthening villi, making crypts deeper and promoting repair of the intestinal mucosa. These effects enable patients with short bowel syndrome to increase their absorptive capacity for nutrients and fluids and therefore reduce their parenteral support. 

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Fig 1: Small intestine Anatomy. Cross section of a ileum with Internal villi. Close-up of Epithelial cells with Microvilli. Vector illustration.

Pharmacokinetics

Teduglutide is administered subcutaneously and is rapidly and extensively absorbed leading to maximum concentrations in the plasma reached within 3-5 hours and has a bioavailability of 88%. Teduglutide is distributed into tissues and has a volume of distribution of approximately 26L. The metabolism pathway is not fully understood however it is expected to follow typical peptide metabolism. Teduglutide is expected to be mainly eliminated via the kidney, as the exposure to teduglutide increases with deteriorating renal function whereas exposure is lower in patients with moderate hepatic impairment vs healthy matched controls. Terminal half life is around 2 hours.  

By TeachMeSeries Ltd (2026)

Fig 2: Pharmacokinetics of teduglutide

Cautions, Contraindications and Adverse Effects 

GLP-2 Agonists promote intestinal growth therefore caution should be applied in patients with colonic polyps or history of cancer. A colonoscopy with removal of polyps should be performed at baseline and follow-up colonoscopies are recommended annually for the first two years, and then every five years. This is in addition to upper gastro-intestinal endoscopy before and during treatment with teduglutide to monitor for neoplasia or malignancy.

For the same reason, teduglutide is contraindicated in those with an active or suspected malignancy, or for those who have a history of malignancies in the GI tract including hepatobiliary system and pancreas within the last 5 years.

Teduglutide is also contraindicated in patients with hypersensitivity to the active substance, excipients or trace residues of tetracycline. 

Other side effects reported in clinical trials include: 

• Cholecystitis, cholangitis and cholelithiasis 
• Chronic and acute pancreatitis, pancreas infection, increased blood amylase and lipase
• Intestinal obstruction 
• Fluid and electrolyte imbalance including fluid overload and dehydration; most likely in the first 4 weeks whilst parenteral support is adjusted alongside therapy starting
• Respiratory tract infection 
• Gastrointestinal side effects such as abdominal distention, abdominal pain, nausea and vomiting 
• Injection site reactions – mostly moderate in severity; none led to discontinuation of therapy
• Bulging of stoma 

References

1. Revestive 5 mg powder and solvent for solution for injection – Summary of Product Characteristics (SmPC) – (emc) | 3382 accessed 24/7/25
2. Pironi, L., Arends, J., Baxter, J., Bozzetti, F., Peláez, R. B., Cuerda, C., Forbes, A., Gabe, S., Gillanders, L., Holst, M., Jeppesen, P. B., Joly, F., Kelly, D., Klek, S., Irtun, Ø., Damink, S. O., Panisic, M., Rasmussen, H. H., Staun, M., . . . Shaffer, J. (2014). ESPEN endorsed recommendations. Definition and classification of intestinal failure in adults. Clinical Nutrition, 34(2), 171–180. https://doi.org/10.1016/j.clnu.2014.08.017