Teduglutide

Overview

Short bowel syndrome can follow extensive intestinal loss or dysfunction. The remaining bowel may be unable to absorb enough water, electrolytes and nutrients to maintain health, making parenteral support necessary. Teduglutide was developed to increase the functional contribution of that remaining intestine. The U.S. GATTEX label covers adults and children at least one year old with short bowel syndrome who are dependent on parenteral support. Current prescribing information

GLP-1 and GLP-2 come from the same precursor protein, proglucagon, which explains their similar names. Teduglutide acts at GLP-2 receptors to support intestinal function. Its clinical evidence concerns absorption and intravenous-support requirements in short bowel syndrome; the weight-loss effects of GLP-1 medicines involve a different receptor.

Uses and research areas

The main clinical setting is intestinal failure associated with short bowel syndrome. Trials examine whether support can be safely reduced while nutrition and fluid balance remain adequate. A smaller weekly volume, fewer infusion days and complete independence from support are related outcomes with different consequences. They should be reported separately.

Longer-term work asks how adaptation progresses and whether early volume reductions persist. Pediatric follow-up adds growth and nutritional status to that question. A child may need less parenteral support while still requiring careful attention to weight, body composition and nutrient intake. The recent multicenter pediatric cohort makes this distinction particularly clear.

Mechanism of action

GLP-2 is an intestinal hormone. Drucker and colleagues’ original experiments found that native GLP-2 increased crypt-cell proliferation, bowel weight and villus growth in mice. Crypts generate new lining cells, while villi provide a large surface for absorption. The work supplied a biological reason to study GLP-2 signaling when absorptive capacity is limited. These were native-hormone animal experiments, separate from the later clinical teduglutide trials. Drucker and colleagues, 1996

Teduglutide replaces alanine at position 2 of human GLP-2 with glycine. This makes it less susceptible to breakdown by the enzyme DPP-4 while preserving activity at GLP-2 receptors. Signaling involves several cell types in the intestinal tissue, so an effect on absorption does not require direct activation of every cell that absorbs nutrients. Clinically, improved absorption can allow intravenous support to be reduced under supervision. Label, mechanism and description

Pharmacokinetics

The prescribing information describes subcutaneous teduglutide exposure in specified populations. In healthy subjects, absolute bioavailability was 88%, and peak plasma concentrations occurred about three to five hours after administration. Reported mean terminal half-life was approximately two hours in healthy subjects and 1.3 hours in short bowel syndrome subjects. Those estimates describe plasma teduglutide; intestinal adaptation is a longer biological process. Label, section 12.3

Renal function affects exposure and is addressed in the approved clinical labeling.

Research findings

The earlier randomized trial needed careful endpoint interpretation

Jeppesen and colleagues randomized 83 adults to one of two teduglutide doses or placebo for 24 weeks. The planned response score combined the size, timing and duration of reductions in intravenous support. The higher-dose score did not establish a benefit over placebo; the lower-dose score was favorable in a subsequent exploratory analysis. The planned testing sequence had required success at the higher dose before formally testing the lower dose. Separately, at least 20% less weekly support at both weeks 20 and 24 was achieved by 8 of 32 higher-dose participants, 16 of 35 lower-dose participants and 1 of 16 placebo participants. Jeppesen and colleagues, 2011

STEPS confirmed a sustained reduction in support volume

The subsequent 86-person STEPS trial used a primary response definition of at least a 20% reduction in weekly parenteral-support volume at both weeks 20 and 24. Response occurred in 27 of 43 teduglutide participants (63%) and 13 of 43 placebo participants (30%; P = 0.002). At week 24, mean weekly support-volume reduction was 4.4 ± 3.8 liters with teduglutide versus 2.3 ± 2.7 liters with placebo. Support was adjusted under a common trial process, which helps explain why both groups improved. Jeppesen and colleagues, 2012

The days-off-support result supplied a more practical view of the volume change: 21 of 39 assessed teduglutide participants and 9 of 39 placebo participants reduced support by at least one day per week. These are secondary-outcome denominators, separate from the 43-per-group primary comparison. A volume response did not necessarily mean independence from intravenous nutrition or fluids.

Extension findings showed later gains with attrition

STEPS-2 enrolled 88 adults for longer treatment, with participants and investigators aware that teduglutide was being given. Sixty-five completed the study, and 13 achieved enteral autonomy: adequate nutrition and hydration without intravenous support. Some had already received teduglutide, some switched from placebo, and others entered without prior treatment. These different treatment histories and the loss of participants before completion affect the reported response proportions; the extension had no continuing placebo group. Schwartz and colleagues, 2016

The 2026 pediatric cohort paired support reduction with nutritional concerns

Jimenez and colleagues enrolled 140 children across 14 centers; 120 contributed effectiveness measurements. Over follow-up to three years, the modeled mean reduction in parenteral calories reached 49.5%, and estimated cumulative enteral autonomy reached 32.7%. Weight-for-age and BMI measures declined, and five patients had inflammatory or foveolar polyps. The observational design has no concurrent untreated comparison. It also shows why reducing parenteral calories should be interpreted together with nutritional adequacy. Jimenez and colleagues, 2026

Safety and tolerability

The intended trophic action makes abnormal tissue growth an important concern. The GATTEX label addresses polyps and potential acceleration of neoplastic growth, as well as intestinal obstruction, biliary and pancreatic disease, fluid overload and altered absorption of other medicines. The approved treatment includes clinical surveillance, with adult gastrointestinal evaluation and age-specific pediatric assessments. Prescribing information, warnings

In STEPS-2, common treatment-emergent events included abdominal pain (34%), catheter sepsis (28%) and decreased weight (25%). A treatment-emergent event occurs during observation; these percentages do not establish that teduglutide caused every event. Catheter dependence and the underlying intestinal disease contribute substantial background risk. The extension’s size and lack of a continuing placebo group also limit estimates of uncommon long-term harms. STEPS-2 report

What the research means

Teduglutide has direct controlled evidence for reducing the support burden of short bowel syndrome. The endpoint is useful because intravenous support can occupy many hours and carry complications. Its interpretation still depends on maintaining adequate hydration and nutrition: less prescribed support is beneficial only when the person’s overall needs remain met.

The extension and registry findings broaden the time horizon and show that some participants achieve autonomy after longer treatment. They also preserve the need to account for incomplete follow-up and nutritional decline. The strongest clinical inference comes from combining the randomized support-volume comparison with ongoing assessment of function, growth and safety.

FAQs

Comparisons and related reading

• Larazotide

  Contrasts intestinal absorption and adaptation with experimental barrier-directed therapy in celiac disease.

• KPV

  Examines KPV in laboratory and animal studies of inflammation and intestinal barrier function.

• Semaglutide

  Explains the different GLP-1 receptor biology and outcomes often confused with GLP-2 therapy.

References

Original native-GLP-2 experiments are labelled as biological context. The clinical papers concern teduglutide, while the prescribing information supplies the current approved indication and safety framework.

• Takeda Pharmaceuticals America, Inc. GATTEX (teduglutide) for injection: U.S. prescribing information. DailyMed. Updated September 5, 2025; initial U.S. approval 2012.

  The current official label supplies the exact molecule, U.S. indication, route-specific PK and the growth, obstruction, fluid, biliary/pancreatic and drug-absorption warnings.

• Drucker DJ, Erlich P, Asa SL, Brubaker PL. Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proceedings of the National Academy of Sciences of the United States of America. 1996;93(15):7911–7916. doi:10.1073/pnas.93.15.7911.

  The mouse experiments identified the intestinal growth activity of native GLP-2, providing biological context for the later resistant analogue.

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

  The first 24-week randomized trial had a prespecified hierarchical analysis: the higher-exposure group missed its graded-response endpoint, while the lower group had a favorable comparison.

• Jeppesen PB, Pertkiewicz M, Messing B, Iyer K, Seidner DL, O’Keefe SJD, Forbes A, Heinze H, Joelsson B. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology. 2012;143(6):1473–1481.e3. doi:10.1053/j.gastro.2012.09.007.

  The confirmatory STEPS trial met its support-volume response endpoint. It also reported the separate absolute weekly volume reduction and days-off-support outcome.

• Schwartz LK, O’Keefe SJD, Fujioka K, Gabe SM, Lamprecht G, Pape UF, Li B, Youssef NN, Jeppesen PB. Long-Term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Short Bowel Syndrome. Clinical and Translational Gastroenterology. 2016;7:e142. doi:10.1038/ctg.2015.69.

  The open-label STEPS-2 extension followed longer treatment, attrition and enteral autonomy. Its completer proportions do not supply a new randomized comparison.

• Jimenez L, Ray A, Mercer D, Kocoshis S, Kinberg S, Martinez M, Gumer L, Merritt R, Corkins MR, Vanderpool C, Cohran V, Wendel D, Thompson J, Sudan D, Van Buren KW, Kaufman S, Carey AN, Sabrdaran S, Mitchell P, Dahlberg SE, Weller E, Duggan CP. Safety and long-term effectiveness of teduglutide in children with intestinal failure due to short bowel syndrome: a multicenter, post-marketing cohort study. Pediatric Research. Published online September 17, 2026. doi:10.1038/s41390-026-05489-0.

  The recent post-marketing cohort reports progressive support reduction alongside falling weight/BMI measures and observed polyps, making nutritional monitoring part of the interpretation.

Glossary

Parenteral support

Fluid and/or nutrition delivered intravenously because intestinal absorption is insufficient.

Villus

A projection of the intestinal lining that increases absorptive surface area.

Crypt

A gland-like region of the intestinal lining where epithelial cells are generated.

Enteral autonomy

Maintaining adequate nutrition and hydration without parenteral support.

DPP-4

An enzyme that removes an N-terminal dipeptide from susceptible substrates, including native GLP-2.