Exenatide, a GLP-1 agonist approved for lowering blood glucose concentrations in patients
with type 2 diabetes, has been associated with restoration of the first-phase insulin
response when administered intravenously to patients with type 2 diabetes. In longer clinical
trials, it is associated with progressive decreases in body weight, and improvement in the
dyslipidemia that characterizes insulin resistance, although insulin resistance was not
quantified. The investigators will seek to determine whether exenatide would have similar
effects in individuals who were not diabetic. in particular, the drug effect on beta cell
function and insulin sensitivity would be subject to less confounding by changes in blood
glucose in the prediabetic population, allowing for clearer evaluation of the physiological
effects of the drug on these metabolic endpoints. The investigators will compare 2 groups of
prediabetic insulin resistant individuals, all on a weight loss diet and one group on
exenatide and the other on placebo. The investigators will evaluate restoration of first
phase insulin response, potential glucose lowering effects, including both reversal of
prediabetes and hypoglycemia, and improvement in insulin resistance.