Effect of exenatide on postprandial glucose fluxes, lipolysis, and ß‐cell function in non‐diabetic, morbidly obese patients

Aims: To investigate the effect of exenatide on glucose disposal, insulin secretion, beta-cell function, lipolysis and hormone concentrations in non-diabetic, morbidly obese subjects under physiological conditions. Materials and methods: Patients were assigned to exenatide 10 mu g twice daily (EXE, n = 15) or control (CT, n = 15) for 3 months. Patients received a meal test/tracer study (MTT) to measure endogenous glucose production (EGP), rate of oral glucose appearance (RaO), insulin secretion rate (ISR), beta-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 reduction in body weight (P < .001). The postmeal time-course of glucose, insulin and ISR showed a lower peak between 60 and 180 minutes in phase with a reduction in RaO (P < .01). After an initial similar suppression, EGP resumed at higher rates between 60 and 180 minutes (P =.02) in EXE vs CT, while total RaO and EGP were similar throughout the MTT. In EXE, the postmeal glucagon, GLP1 and GIP responses were reduced (P < .05). Fasting and postprandial lipolysis and beta-cell function were unaltered by active treatment. HIR, AT-IR and IS were all improved after exenatide treatment (P < .05). Conclusions: In morbidly obese non-diabetic subjects, exenatide causes weight loss, decreased postprandial glycaemia and glucagon response without changes in beta-cell function. These effects are consequent upon delayed oral glucose appearance in the circulation. Exenatide treatment is also associated with an improvement in hepatic, adipose tissue and whole-body IS with no influence on postprandial lipolysis.