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TEDUGLUTIDE

Teduglutide is a medication that has been extensively studied for its effectiveness in treating Short Bowel Syndrome (SBS), a condition where patients have insufficient intestinal absorptive capacity, usually due to surgical removal of portions of the small intestine. These patients often depend on parenteral support (PS) – nutrition delivered directly into the bloodstream – for survival. Clinical trials have shown that teduglutide, which is similar to a naturally occurring hormone called glucagon-like peptide 2 (GLP-2), can enhance intestinal absorption, potentially reducing the need for parenteral nutrition. This article summarizes key findings from clinical trials examining teduglutide’s safety, efficacy, and impact on quality of life for patients with Short Bowel Syndrome.

Table of Contents

What is Teduglutide?

Teduglutide is a medication approved for the treatment of Short Bowel Syndrome (SBS) in patients who are dependent on parenteral support. It is known by brand names such as Gattex and Revestive, and is also referred to by other identifiers including TAK-633 and A16AX08 in scientific and medical literature [1].

Teduglutide is a synthetic analog of glucagon-like peptide-2 (GLP-2), which is a naturally occurring hormone in the human body. GLP-2 regulates the functional and structural integrity of cells lining the gastrointestinal tract. By mimicking this hormone, teduglutide helps improve intestinal absorption, which is particularly important for patients with SBS [2].

How Teduglutide Works

Teduglutide works by enhancing the rehabilitation of the intestine through several mechanisms:

  • Increases intestinal blood flow [3]
  • Inhibits gastric secretion [3]
  • Promotes growth of intestinal cells [3]
  • Increases absorption of nutrients [3]
  • Promotes mucosal growth in the gastrointestinal tract [2]
  • Offers protection from inflammation [2]

These effects help improve the body’s ability to absorb nutrients and fluids from food and drink, which is particularly beneficial for patients with SBS who have reduced intestinal absorptive capacity [2].

Conditions Treated with Teduglutide

Short Bowel Syndrome (SBS) is the primary condition for which teduglutide is approved. SBS refers to a malabsorptive disorder mostly caused by surgical interventions, which results in the anatomical and/or functional decrease in small intestinal absorptive capacity. This decrease leads to malabsorption causing malnutrition, dehydration, and weight loss, all of which severely impact a patient’s quality of life [4].

Many patients with SBS require parenteral nutrition (PN) or parenteral support (PS), which means they need to receive nutrition directly into their bloodstream through an intravenous (IV) line. While this can save lives, long-term dependence on PN can lead to serious side effects such as infections and liver damage [5].

Teduglutide has been studied in both adult and pediatric populations with SBS who are dependent on parenteral support [1] [2].

Benefits and Efficacy

Research studies have demonstrated several benefits of teduglutide treatment in patients with SBS:

Reduction in Parenteral Support

One of the primary benefits of teduglutide is its ability to reduce the need for parenteral support in patients with SBS:

  • Studies have shown reductions in parenteral nutrition volume by approximately 20-25% [3] [6]
  • Some studies have reported reductions in PN calories delivered by up to 45% [2]
  • Approximately 20% of patients in clinical trials were able to completely wean off PN during the study period [2]

These reductions are significant because they may decrease the complications associated with long-term parenteral support use [5].

Increased Enteral Nutrition

Teduglutide treatment has been associated with increased enteral nutrition (nutrition taken by mouth or feeding tube) capabilities:

  • Increased enteral nutrition supply in volume by approximately 40% [2]
  • Increased enteral nutrition calories by approximately 62% [2]

Improvements in Intestinal Function

Treatment with teduglutide has been shown to increase plasma citrulline levels, which is a marker of functional intestinal mass. This indicates that teduglutide may actually improve the function of the remaining intestine [2].

How Teduglutide is Administered

Teduglutide is administered as a subcutaneous (under the skin) injection. Specific administration details include:

  • Once-daily injection into one of the four quadrants of the abdomen, or either thigh or arm [1]
  • Injection sites should be rotated with each administration [7]
  • The medication is provided as a lyophilized (freeze-dried) powder that needs to be reconstituted with sterile water before injection [8]

Patients or caregivers will typically be trained on how to properly administer the injection [1].

Dosage Information

The standard dosage of teduglutide for both adults and children with SBS is 0.05 mg/kg body weight once daily [1] [2].

For patients with moderate or severe renal impairment (kidney problems), the dosage may be reduced to 0.025 mg/kg [9].

Treatment duration varies based on clinical response and goals of therapy. In clinical trials, treatment periods have typically ranged from 24 weeks to several years, with some studies evaluating long-term safety and efficacy for up to 3 years or more [10] [11].

Potential Side Effects

Like all medications, teduglutide may cause side effects. Based on clinical trials, common side effects may include:

  • Abdominal pain [12]
  • Nausea [12]
  • Injection site reactions [12]
  • Headache [12]
  • Changes in gastrointestinal function (such as changes in stool output) [12]

More serious but less common side effects may include:

  • Intestinal obstruction [12]
  • Fluid overload [12]
  • Gallbladder and biliary tract disorders [12]
  • Pancreatic disorders [12]

Patients receiving teduglutide are typically monitored for these potential side effects during treatment [12].

Special Populations

Pediatric Patients

Teduglutide has been studied and approved for use in pediatric patients with SBS who are dependent on parenteral support. The recommended dose for children and adolescents (aged 1 to 17 years) is the same as for adults: 0.05 mg/kg body weight once daily [2].

In pediatric studies, teduglutide has shown similar efficacy and safety profiles as in adults. Growth and developmental parameters (weight-for-age, height-for-age, and BMI z-scores) are typically monitored during treatment [13] [14].

Patients with Hepatic or Renal Impairment

For patients with moderate hepatic impairment (liver problems), pharmacokinetic studies suggest that no dose adjustment is needed, as the medication is processed similarly to those with normal hepatic function [15].

For patients with moderate to severe renal impairment (kidney problems), a 50% dose reduction (to 0.025 mg/kg/day) is recommended due to decreased clearance of the medication [16].

Impact on Quality of Life

Beyond the clinical benefits of reducing parenteral support requirements, teduglutide treatment may also improve quality of life for patients with SBS. Studies have examined this aspect with mixed results:

  • Some clinical trials did not show statistically significant improvements in quality of life scores compared to placebo, despite showing improvements from baseline [4]
  • Real-world data suggest that reduction in parenteral support requirements may translate to improved quality of life by decreasing the burden of PN administration and its associated complications [4]
  • Ongoing studies are evaluating quality of life metrics more specifically in pediatric populations using age-appropriate assessment tools [17]

Other Potential Uses of Teduglutide

While teduglutide is primarily approved for SBS, researchers have investigated its potential use in other conditions:

Crohn’s Disease

Some studies have explored the use of teduglutide in patients with Crohn’s disease, examining whether it could help with intestinal healing and symptom management [18] [19].

Graft Versus Host Disease (GVHD)

Preliminary studies have investigated teduglutide’s potential beneficial effects for patients with gastrointestinal signs of GVHD, a condition that can occur after bone marrow transplantation [20].

Enterocutaneous Fistula

Research has also examined teduglutide’s potential to help in the treatment of enterocutaneous fistulas (abnormal connections between the intestine and the skin surface) [21].

Temporary Ileostomy

Studies have investigated whether teduglutide could reduce morbidity and complications in patients with temporary ileostomies [7].

These applications are still being investigated and are not currently approved indications for teduglutide use.

Aspect Details
Drug Name Teduglutide (also known as Gattex, Revestive, TAK-633, ALX-0600)
Primary Indication Short Bowel Syndrome (SBS) in patients dependent on parenteral support
Mechanism of Action Analog of glucagon-like peptide-2 (GLP-2) that increases intestinal blood flow, inhibits gastric secretion, increases growth of intestinal cells, and increases absorption of nutrients
Standard Dosage 0.05 mg/kg body weight administered once daily via subcutaneous injection (0.025 mg/kg for patients with moderate or greater renal impairment)
Key Clinical Trial Findings – Significant reduction in parenteral support volume (20-45% in many studies)
– Reduced frequency of parenteral support (days per week)
– Some patients achieved complete weaning from parenteral support
– Increased plasma citrulline levels (indicator of intestinal function)
– Positive effects on growth parameters in pediatric patients
– Generally well-tolerated safety profile
Study Populations – Adult patients with SBS dependent on parenteral support
– Pediatric patients (4 months to 17 years) with SBS
– Japanese patients (separate studies to confirm efficacy in this population)
– Patients with renal or hepatic impairment (for pharmacokinetic studies)
Common Adverse Events Abdominal pain, nausea, injection site reactions, headaches, gastrointestinal symptoms
Special Monitoring Requirements – Intestinal obstruction
– Fluid overload
– Gallbladder and pancreatic disease
– Development of antibodies against teduglutide
– Potential tumor growth
Additional Research Areas – Treatment of enterocutaneous fistulas
– Effects on temporary ileostomy function
– Treatment of graft-versus-host disease
– Effects on gastrointestinal motor function and permeability
– Impact on lipid metabolism

FAQ

  • What is teduglutide and how does it work? Teduglutide (also known by brand names Gattex and Revestive) is a synthetic analog of glucagon-like peptide 2 (GLP-2), a naturally occurring hormone that regulates the functional and structural integrity of cells lining the gastrointestinal tract. For patients with Short Bowel Syndrome, teduglutide works by increasing intestinal blood flow, inhibiting gastric secretion, promoting growth of intestinal cells, and enhancing nutrient absorption. This helps improve intestinal function and may reduce dependence on parenteral support.
  • What results have clinical trials shown for teduglutide in treating Short Bowel Syndrome? Clinical trials have demonstrated that teduglutide can reduce the volume and frequency of parenteral support (PS) needed by patients with Short Bowel Syndrome. In many studies, patients achieved at least a 20% reduction in weekly PS volume after 24 weeks of treatment. Some patients were even able to completely wean off parenteral support. Trials have also shown increases in plasma citrulline levels (an indicator of functional intestinal mass), improvements in quality of life, and positive effects on nutritional parameters such as body weight.
  • Is teduglutide being studied in pediatric patients? Yes, several clinical trials have studied teduglutide in pediatric patients with Short Bowel Syndrome. These studies evaluate safety, efficacy, pharmacokinetics, and long-term outcomes in children aged from 4 months through 17 years. Results have shown similar benefits to those seen in adults, including reductions in parenteral support volume and frequency. The studies also monitor growth parameters such as height, weight, and BMI z-scores to ensure normal development during treatment.
  • What is the typical dosage of teduglutide used in clinical trials? The most common dosage used in clinical trials is 0.05 mg/kg body weight administered once daily as a subcutaneous injection. This dosage has been studied in both adult and pediatric patients. For patients with moderate to severe renal impairment, a reduced dose of 0.025 mg/kg may be used. The medication is typically injected into the abdomen, thigh, or arm, with injection sites rotated to prevent injection site reactions.
  • What are the potential side effects or safety concerns with teduglutide? Clinical trials have monitored various safety aspects of teduglutide. Common side effects reported include abdominal pain, nausea, injection site reactions, headaches, and gastrointestinal symptoms. More serious concerns being monitored include potential risks of intestinal obstruction, fluid overload, gallbladder and pancreatic disease, and tumor growth (as the drug promotes cell growth). Trials also check for the development of antibodies against teduglutide. However, overall, the medication has shown a manageable safety profile, with most adverse events being mild to moderate in severity.

Ongoing Clinical Trials on TEDUGLUTIDE

  • Study on How Apixaban and Teduglutide Affect Patients with Short Bowel Syndrome on Long-Term Parenteral Nutrition

    Recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium

Glossary

  • Short Bowel Syndrome (SBS): A malabsorptive disorder mostly caused by surgical interventions that result in the removal of a large portion of the small intestine, leading to reduced intestinal absorptive capacity. This can result in chronic intestinal failure requiring parenteral support.
  • Parenteral Support (PS): The delivery of nutrition and fluids directly into the bloodstream (intravenously) rather than through the digestive system. For patients with Short Bowel Syndrome, PS may be necessary for survival but can lead to complications such as infections and liver damage.
  • Teduglutide: A synthetic analog of glucagon-like peptide-2 (GLP-2) that is approved for treating Short Bowel Syndrome in patients dependent on parenteral support. Also known by brand names Gattex and Revestive.
  • GLP-2 (Glucagon-like peptide-2): A naturally occurring hormone that regulates the functional and structural integrity of cells lining the gastrointestinal tract. It plays a role in intestinal growth and function.
  • Enteral Autonomy: The ability to maintain adequate nutrition exclusively through oral or tube feeding without the need for parenteral support. This is often a treatment goal for patients with Short Bowel Syndrome.
  • Parenteral Nutrition (PN): A method of providing nutrition directly into the bloodstream, bypassing the digestive system. It's used when a person cannot receive enough nutrients through eating or tube feeding.
  • Intravenous (IV) Fluids: Liquids given directly into a vein to prevent or treat dehydration, or to provide necessary electrolytes or medications.
  • Pharmacokinetics: The study of how a drug moves through the body, including its absorption, distribution, metabolism, and excretion. This helps determine appropriate dosing and identify potential drug interactions.
  • Subcutaneous Injection: An injection administered beneath the skin into the subcutaneous tissue. Teduglutide is administered via subcutaneous injection, typically into the abdomen, thigh, or arm.
  • Plasma Citrulline: An amino acid whose blood levels can serve as a biomarker for functional intestinal mass. Increases in plasma citrulline may indicate improved intestinal function in response to treatment.
  • Z-score: A statistical measurement that describes a value's relationship to the mean of a group of values. In pediatric studies, Z-scores are used to assess growth parameters like height, weight, and BMI relative to reference populations.
  • Enterocyte Mass: The total amount of cells that line the intestine (enterocytes). These cells are responsible for nutrient absorption, and their mass can be indirectly measured by plasma citrulline levels.
  • Antidrug Antibodies: Antibodies that develop against a therapeutic drug. The development of these antibodies is monitored in clinical trials as they may potentially reduce a drug's effectiveness or cause adverse reactions.
  • Treatment-emergent Adverse Event (TEAE): An adverse event that arises or worsens during treatment with a drug. These events are closely monitored in clinical trials to assess a drug's safety profile.
  • Quality of Life (QoL): A measure of an individual's well-being including physical, mental, and social aspects. In clinical trials, various standardized questionnaires are used to assess how treatments impact quality of life.

References

  1. https://clinicaltrials.gov/study/NCT06973304
  2. https://clinicaltrials.gov/study/NCT03562130
  3. https://clinicaltrials.gov/study/NCT02099084
  4. https://clinicaltrials.gov/study/NCT04733066
  5. https://clinicaltrials.gov/study/NCT00930644
  6. https://clinicaltrials.gov/study/NCT00798967
  7. https://clinicaltrials.gov/study/NCT03953170
  8. https://clinicaltrials.gov/study/NCT00820885
  9. https://clinicaltrials.gov/study/NCT05027308
  10. https://clinicaltrials.gov/study/NCT01560403
  11. https://clinicaltrials.gov/study/NCT05023382
  12. https://clinicaltrials.gov/study/NCT03268811
  13. https://clinicaltrials.gov/study/NCT04832087
  14. https://clinicaltrials.gov/study/NCT02980666
  15. https://clinicaltrials.gov/study/NCT00819468
  16. https://clinicaltrials.gov/study/NCT01028768
  17. https://clinicaltrials.gov/study/NCT02949362
  18. https://clinicaltrials.gov/study/NCT00308438
  19. https://clinicaltrials.gov/study/NCT00072839
  20. https://clinicaltrials.gov/study/NCT04290429
  21. https://clinicaltrials.gov/study/NCT02889393