Piragliatin (RO4389620), a Novel Glucokinase Activator, Lowers Plasma Glucose Both in the Postabsorptive State and after a Glucose Challenge in Patients with Type 2 Diabetes Mellitus: A Mechanistic Study

Context: Glucokinase plays a key role in glucose homeostasis. Glucokinase activators can lower glucose levels in both animal and human type 2 diabetes, but their mechanism of action has never been explored in humans. Objective: The objective of the study was to investigate the effects of the glucokinase activator piragliatin (RO4389620) on β-cell function and glucose fluxes in both fasting and fed (oral glucose tolerance test) states in patients with type 2 diabetes. Design: This was a phase Ib randomized, double-blind, placebo-controlled crossover trial of two (25 and 100 mg) doses of piragliatin. Setting: This study was conducted at a clinical research center. Patients: Patients included 15 volunteer ambulatory patients with mild type 2 diabetes. Interventions: Interventions included three 10-h (−300′ to +300′) studies, with an interval of at least 14 d. Administration of a single dose of placebo or piragliatin 25 mg or piragliatin 100 mg at −120′. Oral glucose tolerance test (at 0′) with dual (iv and o...