In vitro activity: LGD-6972 is a novel and orally available glucagon receptor antagonist that has linear plasma pharmacokinetics consistent with once daily dosing that is comparable in healthy and T2DM subjects. It also reduces plasma glucose in the postprandial state. Dose-dependent increases in fasting plasma glucagon are observed, but glucagon levels decrease and insulin levels increase after an oral glucose load in T2DM subjects. Inhibition of glucagon action by LGD-6972 was associated with decreases in glucose in both healthy and T2DM subjects, the magnitude of which was sufficient to predict improvement in glycaemic control with longer treatment duration in T2DM patients. The safety and pharmacological profile of LGD-6972 after 14 days of dosing supports continued clinical development.