title: Effect of exenatide on gastric emptying and graft survival in islet allograft recipients.
abstract: OBJECTIVE
  To evaluate the effect of exenatide on gastric emptying and long-term metabolic control.
  
  
  METHODS
  Ten islet allograft recipients treated with exenatide up to 4 years. Data from a mixed meal test with (MMT+) versus without (MMT-) administration of exenatide before boost ingestion were analyzed at 6, 12, 24, 36, or 48 months after initiation of exenatide treatment. None of the subjects were symptomatic for gastroparesis before or during the study. The c-peptide, acetaminophen absorption and glucose responses to MMT were analyzed by Student t test and analysis of variance.
  
  
  RESULTS
  Average exenatide dose was 12.75 ± 9.46 μg/dL. The MMT subjects included two groups those with acetaminophen peak ≤120 minutes ("good gastric emptying; n = 4") versus those with an acetaminophen peak ≥180 minutes ("delayed gastric emptying"). Among the MMT+, acetaminophen absorption was the same in both groups (P = .27). Up to 48 months exenatide delayed time to peak of glucose, c-peptide, and acetaminophen as well as suppressed the glucagon response to MMT mean peak: 70.89 ± 12.45 versus 43.24 ± 4.67. The mean values of c-peptide and glucose responses to MMT were not significantly different.
  
  
  CONCLUSIONS
  Long-term exenatide administration up to 4 years was safe in islet transplant recipients, even in the presence of delayed gastric emptying. The effects of exenatide were acute and reversible when the agent was withdrawn. The main difficulty with the use of exenatide in islet transplant subjects is their poor tolerability, although the physiological effects are clearly evident even at low doses. Approximately 63% of total subjects under exenatide treatment discontinued the drug due to nausea and vomiting. The use of new GLP1 analogs with longer half lives and fewer side effects may help to attain higher GLP1 levels, therefore improving islet function and survival.
authors.affiliation: Clinical Cell Transplant Program, Diabetes Research Institute (R-134), Leonard M. Miller School of Medicine, University of Miami, Miami, Florida 33136, USA.
authors.forename: E M L
authors.initials: EM
authors.lastname: Peixoto
authors.forename: T
authors.initials: T
authors.lastname: Froud
authors.forename: L S
authors.initials: LS
authors.lastname: Gomes
authors.forename: L Mireles
authors.initials: LM
authors.lastname: Zavala
authors.forename: A
authors.initials: A
authors.lastname: Corrales
authors.forename: E
authors.initials: E
authors.lastname: Herrada
authors.forename: C
authors.initials: C
authors.lastname: Ricordi
authors.forename: R
authors.initials: R
authors.lastname: Alejandro
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics; D002096:C-Peptide / Q000096:biosynthesis; D017690:Cell Transplantation / Q000379:methods*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D000077270:Exenatide; D005746:Gastric Emptying; D005947:Glucose / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms; D000082:Acetaminophen; D000077270:Exenatide; D005947:Glucose
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