Ranolazine and Its Effects on Hemoglobin A1C

Abstract

Objective: To review the antihyperglycemic effect of ranolazine in type 2 diabetes mellitus (T2DM). Data Sources: An EMBASE search was conducted between January 1966 through December 2015 using the search terms ranolazine, diabetes, and hemoglobin A1C (A1C). Additional references were identified from a review of literature citations. A search of clinicaltrials.gov was conducted to identify unpublished studies assessing ranolazine in diabetes. Study Selection and Data Extraction: All English-language observational and randomized controlled trials assessing the effects of ranolazine on A1C were evaluated. Data Synthesis: Four published and 3 unpublished trials were identified. In all except 1 study, ranolazine 750 to 1000 mg twice daily was associated with a statistically significant decrease in A1C compared with placebo (placebo-corrected change in A1C: −0.28 to −0.7). In the trial in which a significant difference was not observed, patients assigned to ranolazine received a lower maintenance metformin dose compared with patients not assigned to ranolazine. A greater percentage of patients randomized to ranolazine achieved an A1C<7% compared with the placebo group (41.2%-59% vs 25.7%-49%). Ranolazine was not associated with an increase in the incidence of hypoglycemia and was well tolerated overall. The mechanism for lowering of A1C has not been determined. Conclusions: Ranolazine therapy may decrease A1C among patients with T2DM without an increase in hypoglycemia. For patients with T2DM and chronic stable angina, ranolazine may be of use given its utility in cardiovascular disease and benefit in A1C lowering.