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.

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.

Trial registration: ClinicalTrials.gov NCT01472185.

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1

Disposition of subjects. QP, qualifying period.

Figure 2

A: Effect of ranolazine on HbA1c by visit. B: Effect of ranolazine on proportion of subjects achieving HbA1c <7.0%. Placebo, n = 229; ranolazine, n = 227. *P = 0.0046 vs. placebo. †P < 0.0001 vs. placebo. ‡P = 0.0004 vs. placebo.

Figure 3

FSG and glucose response to MMTT at baseline (A) and week 24 (B), as well as PPG change from baseline at weeks 12 and 24 (C). Fasting plasma glucagon and glucagon response to MMTT at baseline (D) and week 24 (E), as well as postprandial glucagon change from baseline at weeks 12 and 24 (F). All values listed are least squares means ± SE.