Introduction: A factor that worsens the course of coronary heart disease (CHD) in patients with type 2 diabetes mellitus (DM2) is cardiovascular autonomic neuropathy (CAN), in which the risk of sudden death increases fivefold. The prevalence of CAN in patients with both CHD and DM2 may reach 60%. Classic cardiovascular tests (CCT) do not permit identification of CAN at the preclinical stage. A modern method of treatment for DM2 uses sodium-glucose co-transporter 2 inhibitors, which have confirmed cardioprotective effects. Aim: To analyze the prevalence of alterations of arterial pressure variability (APV) and of heart rhythm variability (HRV) in patients with both CHD and DM2 and the effect of empagliflozin on these parameters. Materials and methods: A total of 210 patients aged 64.5 6.7 years (103 men) with both CHD and DM2 were examined (group1). Anthropometric and biochemical parameters were analyzed, electrocardiogram and arterial pressure were monitored daily, and CCT was performed. For comparison, 64 patients with CHD with no alterations in the carbohydrate metabolism were examined (group2, n=64, aged 66.4 2.3 years). Further, among patients in group1, patients with impaired HRV and APV were selected, but they had CCT scores 4.0, and they were divided into group1G (n=22) where empagliflozin was added (1025 mg/day) and group1C (n=20) where the previous therapy was continued. Results: CAN was detected in 22% of patients with CHD and DM2, and all patients had impaired HRV and ADV. Deviations of HRV and APV parameters with normal CCT scores ( 4.0) were detected in 43% of the patients. Within 6 months of treatment with empagliflozin, the HbA1c level decreased from 8.38% 0.56% to 6.9% 0.26% (p 0.05); in the groupwithout empagliflozin treatment, it decreased from 8.28% 0.32% to 7.30% 0.29% (p 0.05). In the empagliflozin group, the average heart rate per day decreased from 86.7 2.4 to 76.7 2.1 beats/min (p 0.05), the circadian index increased from 1.19 0.02 to 1.30 0.01 (p 0.05), the SDNN increased from 106.1 2.21 to 114.03 2.34 ms (p 0.05), and the systolic arterial pressure variability index decreased from 22.9% 1.7% to 16.4% 1.9% at daytime (p 0.05) and from 16.8% 2.2% to 12.3% 2.6% at nighttime (p 0.05). Conclusion: The identified alterations of HRV and APV parameters may be manifestations of CAN, and CCT score 4.0 may indicate the preclinical stage. Positive dynamics of HRV and APV was recorded with empagliflozin therapy, which improved the functional condition of the autonomic nervous system.