A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure
David L Sigalet1, Mary E Brindle1, Dana Boctor2
1Pediatric Surgery, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
Insights
Glucagon-like peptide 2 (GLP-2) was well tolerated in infants with intestinal failure, showing potential nutritional benefits. Further research is needed to confirm efficacy and optimal dosing for this pediatric population.
Area of Science:
- Pediatric Gastroenterology
- Pharmacology
- Clinical Nutrition
Background:
- Glucagon-like peptide 2 (GLP-2) analogues are FDA-approved for adults with intestinal failure (IF).
- No prior studies have evaluated GLP-2 in infants with IF.
- This study addresses the gap in knowledge regarding GLP-2 use in pediatric IF.
Purpose of the Study:
- To examine the pharmacokinetics (PK), safety, and nutritional effects of GLP-2 in infants with IF.
- To assess GLP-2 tolerance and PK profiles in a pediatric population.
- To explore potential benefits of GLP-2 on nutritional status in infants.
Main Methods:
- Prospective interventional study involving PN-dependent infants.
- Treatment with varying doses of GLP-2 (5-20 μg/kg/day) for up to 42 days.
- Monitoring of PK, safety, vital signs, and nutritional parameters, with follow-up to one year.
Main Results:
- Six infants (age 5.4±3.2 months) with IF were enrolled.
- GLP-2 was well tolerated with no significant adverse events or changes in vital signs.
- Numerically improved enteral feeds, weight, Z scores, stooling, and citrulline levels were observed.
- PK analysis showed GLP-2 levels of 52-57 pmol/L at 5 μg/kg/day, with no impact on half-life or endogenous GLP-2.
Conclusions:
- GLP-2 demonstrated favorable tolerability and PK in infants with IF, similar to children.
- The findings suggest potential safety and beneficial nutritional effects of GLP-2 in infants.
- Further investigation is warranted to confirm efficacy and optimize use in this population.
Background & Aims:
Glucagon-like peptide 2 (GLP-2) analogues are approved for adults with intestinal failure (IF), but no studies have included infants. This study examined the pharmacokinetics (PK), safety, and nutritional effects of GLP-2 in infants with IF.
Methods:
With parental consent (Health Canada Protocol:150,979), parenteral nutrition (PN)-dependent infants were treated with 5-20-μg/kg/day GLP-2 for 3days (phase 1), and if tolerated continued for 42days (phase 2). Nutritional therapy was by primary caregivers, and follow-up was to one year.
Results:
Six patients were enrolled, age 5.4±3.2months, bowel length: 27±12% of predicted, PN dependent (67±18% of calories). GLP-2 did not affect vital signs, nor were there significant adverse events during the trial. Dosing 5μg/kg/day gave GLP-2 levels of 52-57pmol/L, with no change in half-life or endogenous GLP-2 levels. Enteral feeds, weight, Z scores, stooling frequency, and citrulline levels improved numerically. The trial was discontinued early because of a drop in potency.
Conclusions:
GLP-2 was well tolerated in infants, and pK was similar to children with no changes in endogenous GLP-2 release. The findings suggest that GLP-2 ligands may be safely used in infants and may have beneficial effects on nutritional status. Further study is required.
Level Of Evidence:
2b Prospective Interventional Study.
Related Concept Videos
01:23Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism
01:29Drug Dosing: Infants and Children
01:17Pharmacokinetics in Pediatric Patients: Drug Distribution
01:15Hypoglycemia and Glucagon