title: Effect of ranolazine on A1C and glucose levels in hyperglycemic patients with non-ST elevation acute coronary syndrome.
abstract: OBJECTIVE
  We determined the relationships between glycemia at randomization, concurrent antidiabetic therapy, and change in A1C and fasting plasma glucose (FPG) in patients with diabetes receiving standard treatment for diabetes and randomized to ranolazine or placebo within the MERLIN-TIMI-36 (MERLIN) study. Ranolazine is a novel first-in-class drug approved for treating angina pectoris.
  
  
  METHODS
  Randomization and 4-month glycemic and antidiabetes drug usage data from MERLIN were analyzed using Spotfire and SAS version 9.1 software.
  
  
  RESULTS
  In patients with diabetes and A1C of >or=8-10% at randomization (n = 171), there was an absolute A1C reduction in the ranolazine group of 1.2% (95% CI -1.4 to -1.0), and the placebo-adjusted (n = 182) decrease in A1C by ranolazine was 0.59% (95% CI -0.99 to -0.20, P < 0.001). In patients with FPG of 150-400 mg/dl at randomization, ranolazine (n = 131) compared with placebo (n = 147) reduced FPG by 25.7 mg/dl (95% CI -43.3 to -8.1, P = 0.001). When changes in either A1C or FPG were correlated to A1C or FPG at randomization, the slopes were significantly steeper for ranolazine than placebo (A1C, P = 0.046; FPG, P < 0.001), indicating that lowering of A1C and FPG by ranolazine is related to hyperglycemia at randomization. Ranolazine, compared with placebo, was not associated with serious hypoglycemic events, associated with significant changes in concurrent antidiabetic therapy, or dependent on a history of angina.
  
  
  CONCLUSIONS
  Ranolazine, when added to concurrent antidiabetes treatment, lowers FPG and A1C in patients with cardiovascular disease and poorly controlled diabetes.
authors.affiliation: 1Division of Cardiovascular Therapeutics, Gilead Sciences, Palo Alto, California, USA. jeff.chisholm@gilead.com
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Chisholm
authors.forename: Allison B
authors.initials: AB
authors.lastname: Goldfine
authors.forename: Arvinder K
authors.initials: AK
authors.lastname: Dhalla
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
authors.forename: Ewa
authors.initials: E
authors.lastname: Karwatowska-Prokopczuk
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
mesh_terms: D000083:Acetanilides / Q000494:pharmacology* / Q000627:therapeutic use*; D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use*; D015990:Placebo Effect; D000069458:Ranolazine
chemical_list: D000083:Acetanilides; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010879:Piperazines; D000069458:Ranolazine