TEDUGLUTIDE - A GLP-2 ANALOG IN THE TREATMENT OF SHORT BOWEL SYNDROME: A LITERATURE REVIEW

Authors

DOI:

https://doi.org/10.31435/ijitss.1(49).2026.4880

Keywords:

Teduglutide, GLP-2, Short Bowel Syndrome, Intestinal Failure

Abstract

Short bowel syndrome–associated intestinal failure (SBS-IF) is a rare but severe clinical condition characterized by insufficient intestinal absorptive capacity and frequent dependence on long-term parenteral support. Prolonged reliance on parenteral nutrition is associated with substantial morbidity, underscoring the need for targeted therapeutic strategies that enhance intestinal adaptation and reduce intravenous support requirements. Advances in the understanding of gut-derived trophic hormones have identified glucagon-like peptide-2 (GLP-2) as a key regulator of intestinal growth and function, leading to the development of GLP-2–based pharmacological therapies.

The aim of this narrative literature review is to critically synthesise current evidence regarding the physiological role of GLP-2, the pharmacological properties of teduglutide, and its clinical efficacy and safety in the management of SBS-IF. A comprehensive literature search was conducted using PubMed and Google Scholar, including randomised controlled trials, observational studies, systematic reviews, and meta-analyses relevant to GLP-2 biology and teduglutide therapy.

The available evidence demonstrates that teduglutide enhances intestinal absorptive capacity, promotes mucosal adaptation, and enables clinically meaningful and sustained reductions in parenteral support requirements in both adult and paediatric patients. In selected individuals, treatment may facilitate partial or complete achievement of enteral autonomy. However, given its intestinotrophic mechanism of action, appropriate patient selection, structured monitoring, and long-term safety surveillance remain essential. Overall, teduglutide represents a significant advance in the targeted treatment of SBS-associated intestinal failure.

References

Baccari, M. C., Vannucchi, M. G., & Idrizaj, E. (2024). The possible involvement of glucagon-like peptide-2 in the regulation of food intake through the gut–brain axis. Nutrients, 16(18), Article 3069. https://doi.org/10.3390/nu16183069

Bremholm, L., Hornum, M., Andersen, U. B., Hartmann, B., Holst, J. J., & Jeppesen, P. B. (2011). The effect of glucagon-like peptide-2 on mesenteric blood flow and cardiac parameters in end-jejunostomy short bowel patients. Regulatory Peptides, 168(1), 32–38. https://doi.org/10.1016/j.regpep.2011.03.003

Bremholm, L., Hornum, M., Henriksen, B. M., Larsen, S., & Holst, J. J. (2009). Glucagon-like peptide-2 increases mesenteric blood flow in humans. Scandinavian Journal of Gastroenterology, 44(3), 314–319. https://doi.org/10.1080/00365520802538195

Burrin, D. G., Stoll, B., Petersen, Y., & Sangild, P. (2001a). Glucagon-like peptide 2: A nutrient-responsive gut growth factor. The Journal of Nutrition, 131(3), 709–712. https://doi.org/10.1093/jn/131.3.709

Burrin, D. G., Stoll, B., Petersen, Y., & Sangild, P. (2001b). Glucagon-like peptide 2: A nutrient-responsive gut growth factor. The Journal of Nutrition, 131(3), 709–712. https://doi.org/10.1093/jn/131.3.709

Cani, P. D., Possemiers, S., Van de Wiele, T., Guiot, Y., Everard, A., Rottier, O., Geurts, L., Naslain, D., Neyrinck, A., Lambert, D. M., Muccioli, G. G., & Delzenne, N. M. (2009). Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut, 58(8), 1091–1103. https://doi.org/10.1136/gut.2008.165886

Drucker, D. J. (2002). Gut adaptation and the glucagon-like peptides. Gut, 50(3), 428–435. https://doi.org/10.1136/gut.50.3.428

Drucker, D. J., & Yusta, B. (2014). Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2. Annual Review of Physiology, 76(1), 561–583. https://doi.org/10.1146/annurev-physiol-021113-170317

Dubé, P. E., & Brubaker, P. L. (2007a). Frontiers in glucagon-like peptide-2: Multiple actions, multiple mediators. American Journal of Physiology-Endocrinology and Metabolism, 293(2), E460–E465. https://doi.org/10.1152/ajpendo.00149.2007

Dubé, P. E., & Brubaker, P. L. (2007b). Frontiers in glucagon-like peptide-2: Multiple actions, multiple mediators. American Journal of Physiology-Endocrinology and Metabolism. https://doi.org/10.1152/ajpendo.00149.2007

Dubé, P. E., Forse, C. L., Bahrami, J., & Brubaker, P. L. (2006). The essential role of insulin-like growth factor-1 in the intestinal tropic effects of glucagon-like peptide-2 in mice. Gastroenterology, 131(2), 589–605. https://doi.org/10.1053/j.gastro.2006.05.055

Eliasson, J., Hvistendahl, M. K., Freund, N., Bolognani, F., Meyer, C., & Jeppesen, P. B. (2022). Apraglutide, a novel once-weekly glucagon-like peptide-2 analog, improves intestinal fluid and energy absorption in patients with short bowel syndrome: An open-label phase 1 and 2 metabolic balance trial. JPEN. Journal of Parenteral and Enteral Nutrition, 46(7), 1639–1649. https://doi.org/10.1002/jpen.2362

ESPEN. (2023). ESPEN guideline on chronic intestinal failure in adults: Update 2023. https://www.espen.org/files/ESPEN-Guidelines/ESPEN_guideline_on_chronic_intestinal_failure_in_adults.pdf

ESPGHAN. (n.d.). Medical management of short bowel syndrome-associated intestinal failure (SBS-IF). https://www.espghan.org/dam/jcr:6ba6251e-67fd-47d1-9cc6-d3b352b1a30e/Medical%20Management%20of%20Short%20Bowel%20Syndrome-Associated%20Intestinal%20Failure%20(SBS-IF).pdf

Estall, J. L., & Drucker, D. J. (2006). Glucagon-like peptide-2. Annual Review of Nutrition, 26(1), 391–411. https://doi.org/10.1146/annurev.nutr.26.061505.111223

Drugs.com. (n.d.). FDA approves Gattex (teduglutide) for children 1 year of age and older with short bowel syndrome (SBS). Retrieved December 30, 2025, from https://www.drugs.com/newdrugs/fda-approves-gattex-teduglutide-children-1-year-age-older-short-bowel-syndrome-sbs-4976.html

Drugs.com. (n.d.). FDA approves Gattex to treat short bowel syndrome. Retrieved December 30, 2025, from https://www.drugs.com/newdrugs/fda-approves-gattex-short-bowel-syndrome-3609.html

Gigola, F., Cianci, M. C., Cirocchi, R., Ranucci, M. C., Del Riccio, M., Coletta, R., & Morabito, A. (2022). Use of teduglutide in children with intestinal failure: A systematic review. Frontiers in Nutrition, 9, Article 866518. https://doi.org/10.3389/fnut.2022.866518

Guan, X., Stoll, B., Lu, X., Tappenden, K. A., Holst, J. J., Hartmann, B., & Burrin, D. G. (2003). GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets. Gastroenterology, 125(1), 136–147. https://doi.org/10.1016/S0016-5085(03)00667-X

Dickey, J. (2025). Management of the short bowel syndrome patient [Presentation slides]. ASPEN - American Society for Parenteral and Enteral Nutrition. https://nutritioncare.org/wp-content/uploads/2025/04/VASPEN-Short-Bowel-Presentation_Dickey.pdf

Jeppesen, P. B. (2012). Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome. Therapeutic Advances in Gastroenterology, 5(3), 159–171. https://doi.org/10.1177/1756283X11436318

Jeppesen, P. B. (2014a). Pharmacologic options for intestinal rehabilitation in patients with short bowel syndrome. Journal of Parenteral and Enteral Nutrition, 38(1 Suppl.). https://doi.org/10.1177/0148607114526241

Jeppesen, P. B. (2014b). Spectrum of short bowel syndrome in adults: Intestinal insufficiency to intestinal failure. Journal of Parenteral and Enteral Nutrition, 38(1 Suppl.). https://doi.org/10.1177/0148607114520994

Jeppesen, P. B., Gilroy, R., Pertkiewicz, M., Allard, J. P., Messing, B., & O’Keefe, S. J. (2011). Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut, 60(7), 902–914. https://doi.org/10.1136/gut.2010.218271

Jeppesen, P. B., Hartmann, B., Thulesen, J., Graff, J., Lohmann, J., Hansen, B. S., Tofteng, F., Poulsen, S. S., Madsen, J. L., Holst, J. J., & Mortensen, P. B. (2001). Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon. Gastroenterology, 120(4), 806–815. https://doi.org/10.1053/gast.2001.22555

Jeppesen, P. B., Lund, P., Gottschalck, I. B., Nielsen, H. B., Holst, J. J., Mortensen, J., Poulsen, S. S., Quistorff, B., & Mortensen, P. B. (2009). Short bowel patients treated for two years with glucagon-like peptide 2: Effects on intestinal morphology and absorption, renal function, bone and body composition, and muscle function. Gastroenterology Research and Practice, 2009, Article 616054. https://doi.org/10.1155/2009/616054

Jeppesen, P. B., Pertkiewicz, M., Messing, B., Iyer, K., Seidner, D. L., O’Keefe, S. J. D., Forbes, A., Heinze, H., & Joelsson, B. (2012a). Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology, 143(6), 1473–1481.e3. https://doi.org/10.1053/j.gastro.2012.09.007

Jeppesen, P. B., Pertkiewicz, M., Messing, B., Iyer, K., Seidner, D. L., O’Keefe, S. J. D., Forbes, A., Heinze, H., & Joelsson, B. (2012b). Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology, 143(6), 1473–1481.e3. https://doi.org/10.1053/j.gastro.2012.09.007

Jeppesen, P. B., Vanuytsel, T., Subramanian, S., Joly, F., Wanten, G., Lamprecht, G., Kunecki, M., Rahman, F., Nielsen, T. S. S., Berner-Hansen, M., Pape, U.-F., & Mercer, D. F. (2025). Glepaglutide, a long-acting glucagon-like peptide-2 analogue, reduces parenteral support in patients with short bowel syndrome: A phase 3 randomized controlled trial. Gastroenterology, 168(4), 701–713.e6. https://doi.org/10.1053/j.gastro.2024.11.023

Joly, F., Seguy, D., Nuzzo, A., Chambrier, C., Beau, P., Poullenot, F., Thibault, R., Armengol Debeir, L., Layec, S., Boehm, V., Lallemand, J., Quilliot, D., & Schneider, S. M. (2020). Six-month outcomes of teduglutide treatment in adult patients with short bowel syndrome with chronic intestinal failure: A real-world French observational cohort study. Clinical Nutrition, 39(9), 2856–2862. https://doi.org/10.1016/j.clnu.2019.12.019

Kocoshis, S. A., Merritt, R. J., Hill, S., Protheroe, S., Carter, B. A., Horslen, S., Hu, S., Kaufman, S. S., Mercer, D. F., Pakarinen, M. P., Venick, R. S., Wales, P. W., & Grimm, A. A. (2020). Safety and efficacy of teduglutide in pediatric patients with intestinal failure due to short bowel syndrome: A 24-week, phase III study. JPEN. Journal of Parenteral and Enteral Nutrition, 44(4), 621–631. https://doi.org/10.1002/jpen.1690

Lafferty, R. A., O’Harte, F. P. M., Irwin, N., Gault, V. A., & Flatt, P. R. (2021). Proglucagon-derived peptides as therapeutics. Frontiers in Endocrinology, 12, Article 689678. https://doi.org/10.3389/fendo.2021.689678

Wøjdemann, M., Wettergren, A., Hartmann, B., & Holst, J. J. (1998). Glucagon-like peptide-2 inhibits centrally induced antral motility in pigs. Scandinavian Journal of Gastroenterology, 33(8), 828–832. https://doi.org/10.1080/00365529850171486

Marier, J.-F., Beliveau, M., Mouksassi, M.-S., Shaw, P., Cyran, J., Kesavan, J., Wallens, J., Zahir, H., Wells, D., & Caminis, J. (2008a). Pharmacokinetics, safety, and tolerability of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, following multiple ascending subcutaneous administrations in healthy subjects. The Journal of Clinical Pharmacology, 48(11), 1289–1299. https://doi.org/10.1177/0091270008320605

Marier, J.-F., Beliveau, M., Mouksassi, M.-S., Shaw, P., Cyran, J., Kesavan, J., Wallens, J., Zahir, H., Wells, D., & Caminis, J. (2008b). Pharmacokinetics, safety, and tolerability of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, following multiple ascending subcutaneous administrations in healthy subjects. The Journal of Clinical Pharmacology, 48(11), 1289–1299. https://doi.org/10.1177/0091270008320605

Marier, J.-F., Mouksassi, M.-S., Gosselin, N. H., Beliveau, M., Cyran, J., & Wallens, J. (2010). Population pharmacokinetics of teduglutide following repeated subcutaneous administrations in healthy participants and in patients with short bowel syndrome and Crohn’s disease. The Journal of Clinical Pharmacology, 50(1), 36–49. https://doi.org/10.1177/0091270009342252

Moran, A. W., Al-Rammahi, M. A., Batchelor, D. J., Bravo, D. M., & Shirazi-Beechey, S. P. (2018). Glucagon-like peptide-2 and the enteric nervous system are components of cell-cell communication pathway regulating intestinal Na+/glucose co-transport. Frontiers in Nutrition, 5, Article 101. https://doi.org/10.3389/fnut.2018.00101

Muto, M., Kaji, T., Onishi, S., Yano, K., Yamada, W., & Ieiri, S. (2022). An overview of the current management of short-bowel syndrome in pediatric patients. Surgery Today, 52(1), 12–21. https://doi.org/10.1007/s00595-020-02207-z

Nave, R., Halabi, A., Herzog, R., Schaffer, P., Diefenbach, J., Krause, S., Berghöfer, P., Lahu, G., & Hartmann, M. (2013a). Pharmacokinetics of teduglutide in subjects with renal impairment. European Journal of Clinical Pharmacology, 69(5), 1149–1155. https://doi.org/10.1007/s00228-012-1455-7

Nave, R., Halabi, A., Herzog, R., Schaffer, P., Diefenbach, J., Krause, S., Berghöfer, P., Lahu, G., & Hartmann, M. (2013b). Pharmacokinetics of teduglutide in subjects with renal impairment. European Journal of Clinical Pharmacology, 69(5), 1149–1155. https://doi.org/10.1007/s00228-012-1455-7

Orhan, A., Gögenur, I., & Kissow, H. (2018). The intestinotrophic effects of glucagon-like peptide-2 in relation to intestinal neoplasia. The Journal of Clinical Endocrinology & Metabolism, 103(8), 2827–2837. https://doi.org/10.1210/jc.2018-00655

Pironi, L., Allard, J. P., Joly, F., Geransar, P., Genestin, E., & Pape, U.-F. (2024a). Use of teduglutide in adults with short bowel syndrome-associated intestinal failure. Nutrition in Clinical Practice, 39(1), 141–153. https://doi.org/10.1002/ncp.11015

Pironi, L., Allard, J. P., Joly, F., Geransar, P., Genestin, E., & Pape, U.-F. (2024b). Use of teduglutide in adults with short bowel syndrome-associated intestinal failure. Nutrition in Clinical Practice, 39(1), 141–153. https://doi.org/10.1002/ncp.11015

Pironi, L., Arends, J., Bozzetti, F., Cuerda, C., Gillanders, L., Jeppesen, P. B., Joly, F., Kelly, D., Lal, S., Staun, M., Szczepanek, K., Van Gossum, A., Wanten, G., & Schneider, S. M. (2016). ESPEN guidelines on chronic intestinal failure in adults. Clinical Nutrition, 35(2), 247–307. https://doi.org/10.1016/j.clnu.2016.01.020

Pironi, L., Sasdelli, A. S., Venerito, F. M., Musio, A., Pazzeschi, C., & Guidetti, M. (2021). Candidacy of adult patients with short bowel syndrome for treatment with glucagon-like peptide-2 analogues: A systematic analysis of a single centre cohort. Clinical Nutrition, 40(6), 4065–4074. https://doi.org/10.1016/j.clnu.2021.02.011

Prahm, A. P., Hvistendahl, M. K., Brandt, C. F., Blanche, P., Hartmann, B., Holst, J. J., & Jeppesen, P. B. (2023). Post-prandial secretion of glucagon-like peptide-2 (GLP-2) after carbohydrate-, fat- or protein-enriched meals in healthy subjects. Peptides, 169, Article 171091. https://doi.org/10.1016/j.peptides.2023.171091

Seidner, D. (2018). Reduction of parenteral nutrition and hydration support and safety with long-term teduglutide treatment in patients with short bowel syndrome-associated intestinal failure: STEPS-3 study. Retrieved December 30, 2025, from https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/ncp.10092

Schwartz, L. K., O’Keefe, S. J. D., Fujioka, K., Gabe, S. M., Lamprecht, G., Pape, U.-F., Li, B., Youssef, N. N., & Jeppesen, P. B. (2016a). Long-term teduglutide for the treatment of patients with intestinal failure associated with short bowel syndrome. Clinical and Translational Gastroenterology, 7(2), e142. https://doi.org/10.1038/ctg.2015.69

Schwartz, L. K., O’Keefe, S. J. D., Fujioka, K., Gabe, S. M., Lamprecht, G., Pape, U.-F., Li, B., Youssef, N. N., & Jeppesen, P. B. (2016b). Long-term teduglutide for the treatment of patients with intestinal failure associated with short bowel syndrome. Clinical and Translational Gastroenterology, 7(2), e142. https://doi.org/10.1038/ctg.2015.69

Seidner, D. L., Schwartz, L. K., Winkler, M. F., Jeejeebhoy, K., Boullata, J. I., & Tappenden, K. A. (2013). Increased intestinal absorption in the era of teduglutide and its impact on management strategies in patients with short bowel syndrome-associated intestinal failure. Journal of Parenteral and Enteral Nutrition, 37(2), 201–211. https://doi.org/10.1177/0148607112472906

Sigalet, D. L., Bawazir, O., Martin, G. R., Wallace, L. E., Zaharko, G., Miller, A., & Zubaidi, A. (2006). Glucagon-like peptide-2 induces a specific pattern of adaptation in remnant jejunum. Digestive Diseases and Sciences, 51(9), 1557–1566. https://doi.org/10.1007/s10620-006-9077-5

Tappenden, K. A., Edelman, J., & Joelsson, B. (2013). Teduglutide enhances structural adaptation of the small intestinal mucosa in patients with short bowel syndrome. Journal of Clinical Gastroenterology, 47(7), 602–607. https://doi.org/10.1097/MCG.0b013e3182828f57

Pape, U.-F., Iyer, K. R., Jeppesen, P. B., Kunecki, M., Pironi, L., Schneider, S. M., Seidner, D. L., Lee, H.-M., & Caminis, J. (2020). Teduglutide for the treatment of adults with intestinal failure associated with short bowel syndrome: Pooled safety data from four clinical trials. Retrieved December 31, 2025, from https://journals.sagepub.com/doi/full/10.1177/1756284820905766

Takeda. (n.d.). U.S. FDA approves GATTEX® (teduglutide) for children 1 year of age and older with short bowel syndrome (SBS). Retrieved December 29, 2025, from https://www.takeda.com/en-us/newsroom/news-releases/2019/us-fda-approves-gattex-teduglutide-for-children-1-year-of-age-and-older-with-short-bowel-syndrome-sbs/

Vipperla, K., & O’Keefe, S. J. (2013). Study of teduglutide effectiveness in parenteral nutrition-dependent short-bowel syndrome subjects. Expert Review of Gastroenterology & Hepatology, 7(8), 683–687. https://doi.org/10.1586/17474124.2013.842894

Wang, S. Z., & O’Daniel, E. L. (2025). Updates in intestinal failure management. Journal of Clinical Medicine, 14(9), Article 3031. https://doi.org/10.3390/jcm14093031

Wøjdemann, M., Wettergren, A., Hartmann, B., Hilsted, L., & Holst, J. J. (1999). Inhibition of sham feeding-stimulated human gastric acid secretion by glucagon-like peptide-2. The Journal of Clinical Endocrinology & Metabolism, 84(7), 2513–2517. https://doi.org/10.1210/jcem.84.7.5840

Yusta, B., Boushey, R. P., & Drucker, D. J. (2000). The glucagon-like peptide-2 receptor mediates direct inhibition of cellular apoptosis via a cAMP-dependent protein kinase-independent pathway. Journal of Biological Chemistry, 275(45), 35345–35352. https://doi.org/10.1074/jbc.M005510200

Yusta, B., Holland, D., Waschek, J. A., & Drucker, D. J. (2012). Intestinotrophic glucagon-like peptide-2 (GLP-2) activates intestinal gene expression and growth factor-dependent pathways independent of the vasoactive intestinal peptide gene in mice. Endocrinology, 153(6), 2623–2632. https://doi.org/10.1210/en.2012-1069

Downloads

Published

2026-03-30

How to Cite

Kamil Harenza, Mateusz Taranowicz, Olga Kowalczyk, Dominika Zdobylak, Monika Kowalska, Anita Zięba, Michał Domin, Justyna Całka, Katarzyna Ścibisz, & Karolina Ollik. (2026). TEDUGLUTIDE - A GLP-2 ANALOG IN THE TREATMENT OF SHORT BOWEL SYNDROME: A LITERATURE REVIEW. International Journal of Innovative Technologies in Social Science, 3(1(49). https://doi.org/10.31435/ijitss.1(49).2026.4880

Most read articles by the same author(s)