title: Effect of ranolazine on glycaemic control in patients with type 2 diabetes treated with either glimepiride or metformin.
abstract: OBJECTIVE
  To report the results of two phase III trials assessing the efficacy of ranolazine for glycaemic control in patients with type 2 diabetes on metformin or glimepiride background therapy.
  
  
  METHODS
  In two double-blind trials we randomized 431 and 442 patients with type 2 diabetes to ranolazine 1000 mg twice daily versus placebo added to either glimepiride (glimepiride add-on study) or metformin background therapy (metformin add-on study). Patients receiving ranolazine added to metformin had their metformin dose halved (with the addition of a metformin-matched placebo) relative to the placebo group to correct for a metformin-ranolazine pharmacokinetic interaction. The primary endpoint of the trials was the change from baseline in glycated haemoglobin (HbA1c) at week 24.
  
  
  RESULTS
  When added to glimepiride, ranolazine caused a 0.51% least squares mean [95% confidence interval (CI) 0.71, 0.32] decrease from baseline in HbA1c at 24 weeks relative to placebo and roughly doubled the proportion of patients achieving an HbA1c of <7% (27.1 vs 14.1%; p = 0.001). When added to metformin background therapy, there was no significant difference in the 24-week HbA1c change from baseline [placebo-corrected LS mean difference -0.11% (95% CI -0.31, 0.1)].
  
  
  CONCLUSIONS
  Compared with placebo, addition of ranolazine in patients with type 2 diabetes treated with glimepiride, but not metformin, significantly reduced HbA1c over 24 weeks. The decreased dose of metformin used in the metformin add-on study complicates the interpretation of this trial. Whether an effective regimen of ranolazine added to metformin for glycaemic control can be identified remains unclear.
authors.affiliation: Department of Medicine, Division of Endocrinology, University of California San Diego, San Diego, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pettus
authors.affiliation: Gilead Pharmaceuticals, Foster City, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: McNabb
authors.affiliation: Department of Medicine, Division of Endocrinology, University of California San Diego, San Diego, CA, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Eckel
authors.affiliation: Department of Medicine, Division of Endocrinology, University of California San Diego, San Diego, CA, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Skyler
authors.affiliation: Gilead Pharmaceuticals, Foster City, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dhalla
authors.affiliation: Gilead Pharmaceuticals, Foster City, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Guan
authors.affiliation: Gilead Pharmaceuticals, Foster City, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Jochelson
authors.affiliation: Gilead Pharmaceuticals, Foster City, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Belardinelli
authors.affiliation: Department of Medicine, Division of Endocrinology, University of California San Diego, San Diego, CA, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Henry
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004347:Drug Interactions; D016903:Drug Monitoring; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006442:Glycated Hemoglobin / Q000037:antagonists & inhibitors; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D000069458:Ranolazine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D026941:Sodium Channel Blockers / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000069458:Ranolazine; D026941:Sodium Channel Blockers; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human; C057619:glimepiride
keywords: antidiabetic drug; clinical trial; glycaemic control; randomized trial; type 2 diabetes