TY - JOUR

T1 - Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure

AU - Sigalet, David L

AU - Brindle, Mary

AU - Boctor, Dana

AU - Casey, Linda

AU - Dicken, Bryan

AU - Butterworth, Sonia

AU - Lam, Viona

AU - Karnik, Vikram

AU - de Heuvel, Elaine

AU - Hartmann, Bolette

AU - Holst, Jens

N1 - © 2015 American Society for Parenteral and Enteral Nutrition.

PY - 2017

Y1 - 2017

N2 - BACKGROUND AND AIMS: A glucagon-like peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure.METHODS: Native human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year.RESULTS: Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24% ± 4% of predicted). All were parenteral nutrition dependent since birth, receiving 44% ± 5% of calories by parenteral nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement in Z scores and citrulline levels; the Z score was maintained while citrulline levels returned to baseline once GLP-2 was discontinued.CONCLUSIONS: GLP-2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP-2 release or metabolism. These results suggest that GLP-2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.

AB - BACKGROUND AND AIMS: A glucagon-like peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure.METHODS: Native human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year.RESULTS: Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24% ± 4% of predicted). All were parenteral nutrition dependent since birth, receiving 44% ± 5% of calories by parenteral nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement in Z scores and citrulline levels; the Z score was maintained while citrulline levels returned to baseline once GLP-2 was discontinued.CONCLUSIONS: GLP-2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP-2 release or metabolism. These results suggest that GLP-2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.

U2 - 10.1177/0148607115609566

DO - 10.1177/0148607115609566

M3 - Journal article

C2 - 26471991

VL - 41

SP - 844

EP - 852

JO - Journal of Parenteral and Enteral Nutrition

JF - Journal of Parenteral and Enteral Nutrition

SN - 0148-6071

IS - 5

ER -