title: The use of exenatide in islet transplant recipients with chronic allograft dysfunction: safety, efficacy, and metabolic effects.
abstract: BACKGROUND
  A current limitation of islet transplantation is reduced long-term graft function. The glucagon-like peptide-1 receptor agonist, exenatide (Byetta, Amylin Pharmaceuticals, CA) has properties that could improve existing islet function, prevent further loss of islet mass and possibly even stimulate islet regeneration.
  
  
  METHODS
  This prospective study evaluated the safety, efficacy, and metabolic effects of exenatide in subjects with type 1 diabetes mellitus and islet allograft dysfunction requiring exogenous insulin.
  
  
  RESULTS
  Sixteen subjects commenced exenatide, 12 continue (follow-up 214+/-57 days; range 108-287), four (25%) discontinued medication because of side effects. At 6 months, exogenous insulin was significantly reduced with stable glycemic control (0.15+/-0.02 vs. 0.11+/-0.025 U/kg per day; P<0.0001); three subjects discontinued insulin from 4, 5, and 9 U/day, respectively, two sustained insulin independence with A1c reduction below graft dysfunction criteria. Postprandial capillary blood glucose was significantly decreased (129.4+/-3.8 vs. 118.7+/-4.6 mg/dL; P<0.001), C-peptide and C-peptide-to-glucose ratio increased significantly by 5th and 6th months of treatment (ratio, 1.09+/-0.15 vs. 1.52+/-0.18; P<0.05). Weight loss more than 3 kg occurred in 8 of 12 (67%) subjects. Stimulation testing demonstrated improved glucose disposal and C-peptide secretion (glucose area under the curve 52,332+/-3,219 vs. 42,072+/-1,965; P=0.002 mg x min x dL, mixed meal stimulation index 0.50+/-0.06 vs. 0.66+/-0.09; P=0.03 pmol x mL), with marked suppression of glucagon secretion and progressive increase in amylin secretion. Side effects were more frequent and severe compared with published reports in type 2 diabetes, tolerated doses were lower.
  
  
  CONCLUSIONS
  Exenatide was tolerated in this patient population after appropriate dose titration and there appeared to be gradual but sustained positive effects on glycemic control and islet graft function.
authors.affiliation: Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Froud
authors.forename: Raquel N
authors.initials: RN
authors.lastname: Faradji
authors.forename: Antonello
authors.initials: A
authors.lastname: Pileggi
authors.forename: Shari
authors.initials: S
authors.lastname: Messinger
authors.forename: David A
authors.initials: DA
authors.lastname: Baidal
authors.forename: Gaston M
authors.initials: GM
authors.lastname: Ponte
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Cure
authors.forename: Kathy
authors.initials: K
authors.lastname: Monroy
authors.forename: Armando
authors.initials: A
authors.lastname: Mendez
authors.forename: Gennaro
authors.initials: G
authors.lastname: Selvaggi
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Alejandro
mesh_terms: D000328:Adult; D000682:Amyloid / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D000077270:Exenatide; D005240:Feasibility Studies; D005934:Glucagon / Q000097:blood; D006084:Graft Rejection / Q000378:metabolism / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D058228:Islet Amyloid Polypeptide; D016381:Islets of Langerhans Transplantation; D008875:Middle Aged; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D010455:Peptides; D014688:Venoms; D005934:Glucagon; D000077270:Exenatide