Effect of ranolazine monotherapy on glycemic control in subjects with type 2 diabetes

Robert H. Eckel, Robert R. Henry, Patrick Yue, Arvinder Dhalla, Pamela Wong, Philip Jochelson, Luiz Belardinelli, Jay S. Skyler

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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. RESEARCH DESIGN AND 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.

Original languageEnglish (US)
Pages (from-to)1189-1196
Number of pages8
JournalDiabetes care
Issue number7
StatePublished - Jul 2015

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing


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