Introduction

Teduglutide is a glucagon-like peptide-2 (GLP-2) analogue that has been approved for the treatment of patients ≥1 year of age with short bowel syndrome (SBS) who are dependent on parenteral support. SBS is a rare malabsorptive condition of the gastrointestinal (GI) tract characterized by diarrhea or high ostomy output, malnutrition, and dehydration. It can result in SBS-associated intestinal failure (SBS-IF), requiring intravenous supplementation (IVS) of macronutrients, fluids, and electrolytes (FEs) to maintain nutrition status[1].

Teduglutide is a dipeptidyl-peptidase, degradation-resistant GLP-2 analogue. Recent studies have demonstrated that repeated administration enhances the intestine's functional and structural capacity. Jeppesen et al. showed in a phase III placebo-controlled trial that 63% of patients receiving teduglutide were able to reduce PS volume by ≥20% after 24 weeks[2]. Since then, several studies have demonstrated the efficacy of teduglutide. Nevertheless, a significant discrepancy in success rates can be noted when comparing enteral autonomy rates ranging from 12% to 28%.

Mechanism of action

Teduglutide is the first drug approved by the FDA for long-term treatment of SBS and has shown effectiveness in different clinical trials. Teduglutide binds to and activates the glucagon-like peptide-2 receptor (GLP2R) to release intestinal mediators to increase intestinal and portal blood flow, inhibit gastric acid secretion and decrease intestinal motility.

Adverse effects

The limitations of teduglutide therapy have to be acknowledged. Common adverse effects of teduglutide include abdominal pain (34%), stoma enlargement if a stoma is present (33%), nausea (19%), abdominal distention (16%), injection site reactions (25%), fluid overload (14%), and bowel obstruction (11%). Special attention should be paid to the possibility of the coexisting conditions that may contribute to the previously mentioned symptoms, such as active Crohn disease, intestinal stricture, or bacterial overgrowth.

Contraindications

All contraindications, warnings, and precautions from the summary of product characteristics document for teduglutide must be considered before initiating therapy. Teduglutide is contraindicated in patients with active malignancy and those with a history of malignancy in the GI tract, hepatobiliary tract, or both, including the pancreas, within the past 5 years. Patients with signs and symptoms of small bowel obstruction should be evaluated prior to initiating treatment with teduglutide. Colonoscopy, abdominal ultrasound, and gastroscopy are performed on all patients before the initiation of teduglutide treatment to assess for the presence of polyps and to exclude neoplastic disease as well as to clarify unclear anatomic situations or disease activity in the GI remnant (eg, Crohn's disease). In some situations, further imaging studies may be required, such as small bowel follow-through or computed tomography/magnetic resonance enterography[3]. A post hoc analysis of data from the STEPS study series investigating colon polyps before and after teduglutide treatment reported a polyp detection rate of 12% in patients with SBS-IF aged 39–75 years. Although this rate falls in the lower range of the detection rate in the general patient population with SBS-IF, it supported the recommendation for polyp screening via colonoscopies before and during treatment, as the identification of any cancers at baseline would preclude patients from initiating teduglutide therapy. Furthermore, it would allow for the detection and removal of polyps at risk of progression following the initiation of teduglutide treatment. Despite this recommendation, a retrospective analysis of a large population-based commercial database found that, between 2015 and 2019, 170 adult patients with SBS-IF were prescribed teduglutide, of whom 47% did not have a colonoscopy prior to initiating therapy. Recent care reports showed the de novo development of upper GI adenomas in patients receiving teduglutide, so a gastroscopy before and during teduglutide treatment is advised.

References

[1] Ali Akbar Alizadeh. “Expression, Purification and Characterization of Functional Teduglutide Using GST Fusion System in Prokaryotic Cells.” Advanced pharmaceutical bulletin 13 3 (2023): 592–600.

[2] Felix Harpain. “Teduglutide in short bowel syndrome patients: A way back to normal life?” Journal of Parenteral and Enteral Nutrition 46 2 (2021): 300–309.

[3] Loris Pironi. “Use of teduglutide in adults with short bowel syndrome-associated intestinal failure.” Nutrition in Clinical Practice (2024): 141–153.