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

Camastra, Stefania; Astiarraga, Brenno; Tura, Andrea; Frascerra, Silvia; Ciociaro, Demetrio; Mari, Andrea; Gastaldelli, Amalia; Ferrannini, Ele

Aims To investigate the effect of exenatide on glucose disposal, insulin secretion, ß-cell function, lipolysis and hormone concentrations in non-diabetic, morbidly obese subjects under physiological conditions. Materials and methods Patients were assigned to exenatide 10 µg 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), 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 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 ß-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 ß-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.

EXENATIDE; LIPOLYSIS; PANCREATIC beta cells; OVERWEIGHT persons; GLUCOSE in the body; HEALTH

Diabetes, Obesity & Metabolism, 2017, Vol 19, Issue 3, p412

1462-8902

Academic Journal

10.1111/dom.12836