Teduglutide in intestinal adaptation and repair: light at the end of the tunnel.
BACKGROUND
Malabsorption of nutrients, fluids and electrolytes is a key finding in patients with short bowel syndrome. If not compensated for by increased intake, it leads to diminished body stores and subclinical, and eventually clinical, deficiencies. Until recently, management options were limited to interventions aimed at provision of adequate macro- and micronutrients and fluids to prevent malnutrition, nutrient deficiencies and dehydration, treatment of associated infections and correction and prevention of acid-base disturbances. Identification of novel gut hormones, combined with the growing understanding of their pivotal role in intestinal adaptation, has provoked interest in developing more specific therapies.


OBJECTIVE
To provide an update on the recent advances on the use of teduglutide in patients with short bowel syndrome.


METHODS
A comprehensive Medline search using the terms teduglutide, ALX-0600, dipeptidyl peptidase IV (DPP-IV) and glucagon like peptide-2 (GLP-2).


RESULTS
Teduglutide (GATTEX, ALX-0600; NPS Allelix Corp) is a synthetic DPP-IV-resistant recombinant human GLP-2 analog that differs from GLP-2 only by an N-terminus substitution of glycine for alanine in position 2 of the peptide that renders the component resistant to enzymatic degradation. Based on the results of the few Phase II studies and the preliminary results of a Phase III trial, teduglutide at doses of 0.05 or 0.10 mg/kg/day may improve many clinical, laboratory and histologic abnormalities in short bowel syndrome patients. It appears to be safe and well tolerated.


CONCLUSIONS
Teduglutide is a first-in-class therapy with the potential to create a new standard of care for patients suffering from short bowel syndrome. Future studies to address the appropriate initial and maintenance dosage and optimal duration of treatment are needed.
Mardini
Houssam E
HE
University of Kentucky Chandler Medical Center, Division of Digestive Diseases and Nutrition, 800 Rose Street, Rm MN649, Lexington, KY 40536, USA.
de Villiers
Willem J S
WJ
D000222:Adaptation, Physiological / Q000187:drug effects* / Q000502:physiology; D000328:Adult; D019943:Amino Acid Substitution; D001835:Body Weight / Q000187:drug effects; D002648:Child; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D003424:Crohn Disease / Q000188:drug therapy; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology; D005768:Gastrointestinal Hormones / Q000502:physiology; D053767:Glucagon-Like Peptide 2 / Q000737:chemistry / Q000493:pharmacokinetics / Q000502:physiology / Q000627:therapeutic use / Q000633:toxicity; D006207:Half-Life; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D008658:Inactivation, Metabolic; D007408:Intestinal Absorption / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012778:Short Bowel Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D005768:Gastrointestinal Hormones; D053767:Glucagon-Like Peptide 2; D010455:Peptides; D011994:Recombinant Proteins; D019382:Human Growth Hormone; C494910:teduglutide; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4