Research Article Ranolazine Improves Glycemic Variability and Endothelial Function in Patients with Diabetes and Chronic Coronary Syndromes: Results from an Experimental Study Annunziata Nusca , 1 Federico Bernardini, 1 Fabio Mangiacapra, 1 Ernesto Maddaloni, 2 Rosetta Melfi, 1 Elisabetta Ricottini, 1 Francesco Piccirillo, 1 Silvia Manfrini, 3 Gian Paolo Ussia, 1 and Francesco Grigioni 1 1 Unit of Cardiac Sciences, Department of Medicine, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy 2 Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy 3 Unit of Endocrinology and Diabetes, Department of Medicine, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy Correspondence should be addressed to Annunziata Nusca; a.nusca@unicampus.it Received 12 August 2021; Revised 25 November 2021; Accepted 13 December 2021; Published 31 December 2021 Academic Editor: Munmun Chattopadhyay Copyright © 2021 Annunziata Nusca et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Ranolazine is a second-line drug for the management of chronic coronary syndromes (CCS). Glucose-lowering and endothelial effects have also been reported with this agent. However, whether ranolazine may improve short-term glycemic variability (GV), strictly related to the prognosis of patients with type 2 diabetes (T2D), is unknown. Thus, we aimed to explore the effects of adding ranolazine to standard anti-ischemic and glucose-lowering therapy on long- and short-term GV as well as on endothelial function and oxidative stress in patients with T2D and CCS. Methods. Patients starting ranolazine (n = 16) were evaluated for short-term GV, haemoglobin 1Ac (Hb1Ac) levels, endothelial-dependent flow-mediated vasodilation (FMD), and oxidative stress levels at enrolment and after 3-month follow-up. The same measurements were collected from 16 patients with CCS and T2D that did not receive ranolazine, matched for age, gender, and body mass index. Results. A significant decline in Hb1Ac levels was reported after 3-month ranolazine treatment (mean change -0.60%; 2-way ANOVA p =0:025). Moreover, among patients receiving ranolazine, short-term GV indexes were significantly improved over time compared with baseline (p =0:001 for time in range; 2-way ANOVA p =0:010). Conversely, no significant changes were reported in patients without ranolazine. Finally, greater FMD and lower oxidative stress levels were observed in patients on ranolazine at 3 months. Conclusions. Ranolazine added to standard anti-ischemic and glucose-lowering therapy demonstrated benefit in improving the glycemic status of patients with T2D and CCS. How this improvement contributes to the overall myocardial benefit of ranolazine requires further studies. 1. Background Ranolazine mainly exerts its anti-ischemic effects by inhibit- ing the myocardial late sodium current [1]. According to guidelines, it is approved as a second-line treatment in man- aging patients with chronic coronary syndromes (CCS) inadequately controlled by or intolerant to first-line anti- ischemic agents [2]. However, the blockage of late sodium channels by this drug has also been reported in other tissues such as pancreatic islets [3]. Hence, ranolazine significantly lowered fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) levels in diabetic patients naïve to previous antidiabetic medications or already on glucose-lowering agents at least twelve weeks of treatment later, suggesting a specific role of this drug in patients with the coexistence of CCS and type 2 diabetes (T2D) [4–6]. Hindawi Journal of Diabetes Research Volume 2021, Article ID 4952447, 9 pages https://doi.org/10.1155/2021/4952447