Effect of exenatide on postprandial glucose fluxes, lipolysis function in non-diabetic, morbidly obese patients

Aims: To investigate the effect of exenatide on glucose disposal, insulin secretion, ß-cell func-tion, lipolysis and hormone concentrations in non-diabetic, morbidly obese subjects underphysiological conditions.Materials and methods: Patients were assigned to exenatide 10 ?g twice daily (EXE, n = 15) orcontrol (CT, n = 15) for 3 months. Patients received a meal test/tracer study (MTT) to measureendogenous glucose production (EGP), rate of oral glucose appearance (RaO), insulin secretionrate (ISR), ß-cell function, hepatic insulin resistance (HIR) and adipose tissue insulin resistance(AT-IR) and insulin sensitivity (IS).Results: Post treatment, the EXE group showed a significant reducti on in body weight (P < .001).The postmeal time-course of glucose, insulin and ISR showed a lower peak between 60 and180 minutes in phase with a reducti on in RaO (P < .01). After an initial similar suppression, EGPresumed at higher rates between 60 and 180 minutes (P =.02)inEXEvsCT,whiletotalRaOandEGP were similar throughout the MTT. In EXE, the postmeal glucagon, GLP1 and GIP responseswere reduced (P < .05). Fasting and postprandial lipolysis and ß-cell function were unaltered by activetreatment. HIR, AT-IR and IS were all improved after exenatide treatment (P < .05).Conclusions: In morbidly obese non-diabetic subjects, exenatide causes weight loss, decreasedpostprandial glycaemia and glucagon response without changes in ß-cell function. These effectsare consequent upon delayed oral glucose appearance in the circulation. Exenatide treatment isalso associated with an improvement in hepatic, adipose tissue and whole-body IS with noinfluence on postprandial lipolysis.