TY - JOUR
T1 - Effect of exenatide on gastric emptying and graft survival in islet allograft recipients
AU - Peixoto, E. M.L.
AU - Froud, T.
AU - Gomes, L. S.
AU - Zavala, L. Mireles
AU - Corrales, A.
AU - Herrada, E.
AU - Ricordi, C.
AU - Alejandro, R.
N1 - Funding Information:
This work was supported by NIH grants MO1RR16587 , 1RO1-DK55347 , and IU42 RR016603 , Diabetes Research Foundation International 4-200-946 , and the Diabetes Research Institute Foundation. The authors thank the staff of the Clinical Cell Transplant Program for their continued support.
PY - 2011/11
Y1 - 2011/11
N2 - 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 The effects of exenatide were acute and reversible when the agent was withdrawn.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.
AB - 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.
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U2 - 10.1016/j.transproceed.2011.10.022
DO - 10.1016/j.transproceed.2011.10.022
M3 - Article
C2 - 22099764
AN - SCOPUS:81455143467
VL - 43
SP - 3231
EP - 3234
JO - Transplantation Proceedings
JF - Transplantation Proceedings
SN - 0041-1345
IS - 9
ER -