Effect of exenatide on gastric emptying in islet allograft recipients

E. Moraes Leao Peixoto, T. Froud, L. S. Gomes, L. Mireles Zavala, A. Corrales, E. Herrada, C. Ricordi, R. Alejandro
Diabetes Research Institute, University of Miami, Miami, USA

Objective: To evaluate effect of exenatide on gastric emptying and long term metabolic control.

Methods: Ten islet allograft recipients treated with exenatide up to four years were evaluated. Data from mixed meal test with (MMT+) or without (MMT-) administration of exenatide before boost ingestion were analyzed at 6, 12, 24, 36 and 48 months after initiation of exenatide treatment. None of these subjects were symptomatic for gastroparesis before or during the study. The c-peptide, acetaminophen absorption and glucose responses to MMT were analyzed with analysis of variance: T-test and one way ANOVA.

Results: Average exenatide dose was 12.75±9.46mcg/day. In the MMT- two groups were identified, those with acetaminophen peak </= 120 mins, were labeled "good gastric emptying" (n=4) and those with acetaminophen peak >/= 180 mins, "delayed gastric emptying". In the “MMT +” acetaminophen absorption was the same in both groups (P=0.27). Exenatide delayed time to peak of glucose, c-peptide, acetaminophen and suppressed glucagon response to MMT mean peak 70.89±12.45 to 43.24±4.67 up to 48 months. Means of c-peptide and glucose responses to MMT were not significant different.

Conclusions: Long term exenatide administration up to 4 years is safe in islet transplant recipients, even in the presence of delayed gastric emptying. Effects of exenatide are acute and reversible when exenatide administration is stopped. The main difficulty with the use of exenatide in islet transplant subjects is the poor tolerability, although the physiological effects are clearly evident even at lower doses. Approximately 63% of total subjects under exenatide treatment in our center discontinued the drug due to nausea and vomiting. The use of new GLP1 analogs with longer half life, less side effects, may help to attain higher GLP1 levels, therefore improve islet function and survival. At the present time we are evaluating Liraglutide (once daily GLP1) in our subjects.