title: Effects of piragliatin, a glucokinase activator, on fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus.
abstract: To assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of piragliatin, a double-blind, randomized, placebo-controlled, multiple-ascending-doses study was conducted in patients with type 2 diabetes mellitus (T2D). Fifty-nine T2D patients were given piragliatin or placebo in a dose-escalation design as a single dose on day 1 followed by multiple doses on days 3 through 8 at doses of 10, 25, 50, 100, and 200 mg twice a day (BID) as well as 200 mg every day (QD). Blood and urine samples were collected for PK analysis. PD assessments included plasma glucose, insulin, C-peptide, glucagon, and GLP-1. Piragliatin exposure was dose proportional without appreciable accumulation or food effect. Piragliatin treatment at steady state yielded dose-dependent reductions up to 32.5% and 35.5% for the highest dose in fasting and postprandial plasma glucose. Piragliatin was well tolerated. Mild or moderate hypoglycemia with rapid recovery after sugar-containing drinks or scheduled meals was the only dose-limiting adverse event. It is concluded that multiple doses of piragliatin consistently showed rapid, dose-dependent glucose reduction of fasting and postprandial plasma glucose in T2D patients.
authors.affiliation: Roche Innovation Center of New York, New York, NY, USA.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhi
authors.affiliation: Roche Innovation Center of New York, New York, NY, USA.
authors.forename: Suoping
authors.initials: S
authors.lastname: Zhai
mesh_terms: D000328:Adult; D000368:Aged; D044482:Benzeneacetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period
chemical_list: D044482:Benzeneacetamides; D001786:Blood Glucose; D007004:Hypoglycemic Agents; C553963:piragliatin
keywords: glucokinase activator; pharmacodynamics; pharmacokinetics