Dimitris Kounatidis1, Natalia G Vallianou2, Dimitrios Tsilingiris3, Gerasimos Socrates Christodoulatos4, Eleni Geladari1, Theodora Stratigou1, Irene Karampela5, Maria Dalamaga6. 1. Departments of Internal Medicine and Endocrinology, Evangelismos General Hospital, 45-47 Ypsilantou Street, 10676, Athens, Greece. 2. Departments of Internal Medicine and Endocrinology, Evangelismos General Hospital, 45-47 Ypsilantou Street, 10676, Athens, Greece. natalia.vallianou@hotmail.com. 3. First Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, 17 St Thomas Street, 11527, Athens, Greece. 4. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527, Athens, Greece. 5. 2nd Department of Critical Care, Medical School, University of Athens, Attikon General University Hospital, 1 Rimini Street, Chaidari, 12462, Athens, Greece. 6. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527, Athens, Greece. madalamaga@med.uoa.gr.
Abstract
PURPOSE OF REVIEW: Although Glucagon-like peptide (GLP)-1 receptor agonists have been used for almost two decades in the treatment of diabetes mellitus type 2 and, lately, in obesity, recent years have seen an increasing interest in the pharmacological agonism of other proglucagon-derived peptides, including GLP-2. Herein, we aimed to review the available evidence on the effects of GLP-2 agonism from animal and clinical studies. Furthermore, we summarize the current clinical applications of GLP-2 agonists among patients with intestinal failure associated with short bowel syndrome (SBS-IF) as well as potential future expansion of their indications to other intestinal disorders. RECENT FINDINGS: Evidence from preclinical studies has highlighted the cellular trophic and functional beneficial actions of GLP-2 on small intestinal and colonic mucosa. Subsequently, pharmacologic agonism of GLP-2 has gathered interest for the treatment of patients with conditions pertaining to the loss of intestinal anatomical and/or functional integrity to a degree requiring parenteral support, collectively referred to as intestinal failure. GLP-2 analogs positively influence nutrient absorption in animal models and humans, although continued therapy is likely needed for sustained effects. The degradation-resistant GLP-2-analog teduglutide has received approval for the treatment of SBS-IF, in which it may decisively reduce patient dependency on parenteral support and improve quality of life. Another two longer-acting analogs, glepaglutide and apraglutide, are currently undergoing phase III clinical trials. The use of GLP-2 analogs is effective in the management of SBS-IF and may show promise in the treatment of other severe gastrointestinal disorders associated with loss of effective intestinal resorptive surface area.
PURPOSE OF REVIEW: Although Glucagon-like peptide (GLP)-1 receptor agonists have been used for almost two decades in the treatment of diabetes mellitus type 2 and, lately, in obesity, recent years have seen an increasing interest in the pharmacological agonism of other proglucagon-derived peptides, including GLP-2. Herein, we aimed to review the available evidence on the effects of GLP-2 agonism from animal and clinical studies. Furthermore, we summarize the current clinical applications of GLP-2 agonists among patients with intestinal failure associated with short bowel syndrome (SBS-IF) as well as potential future expansion of their indications to other intestinal disorders. RECENT FINDINGS: Evidence from preclinical studies has highlighted the cellular trophic and functional beneficial actions of GLP-2 on small intestinal and colonic mucosa. Subsequently, pharmacologic agonism of GLP-2 has gathered interest for the treatment of patients with conditions pertaining to the loss of intestinal anatomical and/or functional integrity to a degree requiring parenteral support, collectively referred to as intestinal failure. GLP-2 analogs positively influence nutrient absorption in animal models and humans, although continued therapy is likely needed for sustained effects. The degradation-resistant GLP-2-analog teduglutide has received approval for the treatment of SBS-IF, in which it may decisively reduce patient dependency on parenteral support and improve quality of life. Another two longer-acting analogs, glepaglutide and apraglutide, are currently undergoing phase III clinical trials. The use of GLP-2 analogs is effective in the management of SBS-IF and may show promise in the treatment of other severe gastrointestinal disorders associated with loss of effective intestinal resorptive surface area.
Authors: Robert J Heine; Luc F Van Gaal; Don Johns; Michael J Mihm; Mario H Widel; Robert G Brodows Journal: Ann Intern Med Date: 2005-10-18 Impact factor: 25.391