BACKGROUND: The antihyperglycemic effect of the antianginal drug ranolazine has been recently reported. The objective of this systematic review is to summarize the evidence from published literature detailing the impact of high dose ranolazine (1000 mg twice daily) on hemoglobin A1c (HbA1c) levels in patients with diabetes mellitus (DM).

METHODS: A systematic literature search was performed through Feb 2018 using PubMed, EMBASE and Cochrane databases with the following key terms: “'ranolazine'”, “glucose”, “diabetes”, “A1c”, and “glycemic”. The review was restricted to randomized controlled trials published in English in diabetic patients with HbA1c changes reported as study endpoints. Studies using low dose ranolazine (500 mg twice daily) were excluded. The Cochrane Risk of Bias Tool was used to assess bias risk.

RESULTS: Of the initial 180 citations, seven randomized controlled trials involving 3,437 patients were included in this review. A meta‐analysis of four of the seven trials was conducted, showing adding ranolazine to the standard antidiabetic therapy significantly reduced HbA1c levels by 0.47% (95% CI ‐0.57% to ‐0.36%, P < 0.00001) compared to placebo (heterogeneity: P = 0.56; I2 = 0%). Similar results were reported in another study, where ranolazine as monotherapy in patients with uncontrolled DM managed by lifestyle alone reduced HbA1c levels by 0.56% (95% CI ‐0.76% to ‐0.36%, p < 0.0001). Two other studies investigated the relationship between effect of ranolazine and baseline HbA1c, and greater reduction of HbA1c was observed in patients with poorer glycemic control. These results were consistent with the CARISA trial as higher HbA1c reduction was noted in patients taking insulin. Discussion: High dose ranolazine has been shown to have positive antihyperglycemic effects in patients with DM. Ranolazine as adjunct therapy for severe chronic angina may provide additional benefits in patients with comorbid DM and chronic stable angina. Other: Authors have no disclosures.