title: Effect of Ranolazine Monotherapy on Glycemic Control in Subjects With Type 2 Diabetes.
abstract: OBJECTIVE
  Ranolazine is an antianginal drug that mediates its effects by inhibition of cardiac late sodium current. Although ranolazine is not approved for the treatment of type 2 diabetes, in post hoc analyses of pivotal angina trials, ranolazine was associated with reductions in percent glycosylated hemoglobin (HbA1c) in subjects with type 2 diabetes. The study prospectively assessed the safety and efficacy of ranolazine in subjects with type 2 diabetes with inadequate glycemic control managed by lifestyle alone.
  
  
  METHODS
  The study was conducted worldwide in 465 subjects, with baseline HbA1c of 7-10% (53-86 mmol/mol) and fasting serum glucose of 130-240 mg/dL, randomized to placebo versus ranolazine.
  
  
  RESULTS
  Compared with placebo, there was a greater decline in HbA1c at week 24 from baseline (primary end point) in subjects taking ranolazine (mean difference -0.56% [-6.1 mmol/mol]; P < 0.0001). Moreover, the proportion of subjects achieving an HbA1c <7.0% was greater with ranolazine (25.6% vs. 41.2%; P = 0.0004). Ranolazine was associated with reductions in fasting (mean difference -8 mg/dL; P = 0.0266) and 2-h postprandial glucose (mean difference -19 mg/dL; P = 0.0008 vs. placebo). Subjects taking ranolazine trended toward a greater decrease from baseline in fasting insulin (P = 0.0507), a greater decrease in fasting glucagon (P = 0.0003), and a lower postprandial 3-h glucagon area under the curve (P = 0.0031 vs. placebo). Ranolazine was safe and well tolerated.
  
  
  CONCLUSIONS
  Compared with placebo, use of ranolazine monotherapy over 24 weeks, in subjects with type 2 diabetes and inadequate glycemic control on diet and exercise alone, significantly reduced HbA1c and other measures of glycemic control.
authors.affiliation: Divisions of Endocrinology, Metabolism and Diabetes and Cardiology, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO robert.eckel@ucdenver.edu.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Eckel
authors.affiliation: Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.affiliation: Cardiovascular Clinical Research, Gilead Sciences, Foster City, CA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Yue
authors.affiliation: Department of Biology, Cardiovascular Therapeutic Area, Gilead Sciences, Fremont, CA.
authors.forename: Arvinder
authors.initials: A
authors.lastname: Dhalla
authors.affiliation: Cardiovascular Therapeutic Area, Biostatistics, Gilead Sciences, Foster City, CA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Wong
authors.affiliation: Cardiovascular Clinical Research, Gilead Sciences, Foster City, CA.
authors.forename: Philip
authors.initials: P
authors.lastname: Jochelson
authors.affiliation: Cardiovascular Clinical Research, Gilead Sciences, Foster City, CA Department of Biology, Cardiovascular Therapeutic Area, Gilead Sciences, Fremont, CA.
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism, Pediatrics, and Psychology, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Skyler
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069458:Ranolazine / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069458:Ranolazine; C517652:hemoglobin A1c protein, human