Abstract: Objective The aim of this study was to investigate dapagliflozin and metformin combination therapy in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Methods A total of 105 patients with T2DM and NAFLD were encountered in our hospital between March 2023 and March 2025, and were randomly assigned to receive metformin in 52 cases for control, or take oral dapagliflozin and metformin in 53 cases for 24 weeks. Serum fasting insulin (FINS) was detected by electrochemiluminescence, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The area of visceral fat was measured by visceral fat detector. The densities of liver and spleen were detected by CT scanner, and liver to spleen CT ratio was calculated. The heart rate variability indexes, e.g., standard deviation of NN intervals (SDNN), standard deviation of the average NN intervals (SDANN), root mean square of successive differences (rMSSD), percent of NN50 in the total number of NN intervals (pNN50), low frequency (LF) and high frequency (HF) were monitored by 24 h electrocardiogram. Results By end of 24-week treatment, visceral fat area in combination group was(126.6±15.8)cm², much less than [(135.8±17.0)cm²,P<0.05],while liver/spleen CT ratio was (0.9±0.2),much greater than [(0.8±0.2)cm²,P<0.05] in the control; HbA1c, FPG and HOMA-IR were (7.0±0.9)%, (6.0±0.8)mmol/L and (2.2±0.3), all significantly lower than [(7.7±1.0)%, (6.8±0.9)mmol/L and (2.7±0.3), respectively, P<0.05] in the control; SDNN, SDANN, rMSSD, pNN50, LF and HF were (111.2±13.9)ms, (106.9±13.4)ms, (21.9±4.7)ms, (4.2±0.9)%, (801.5±100.2)ms² and (494.8±91.9)ms²,all much higher than [(98.1±12.3)ms, (89.3±11.2)ms, (19.5±4.4)ms, (3.7±0.8)%, (724.9±90.6)ms² and (415.6±82.0)ms², respectively, P<0.05] in the control group. Conclusion Combination of dapagliflozin and metformin in treatment of patients with T2DM and NAFLD could significantly improve glucose metabolism, reduce visceral fat, and improve autonomic nerve functions.

Key words: Non-alcoholic fatty liver disease, Type 2 diabetes mellitus, Dapagliflozin, Metformin, Autonomic nerve functions, Therapy