Abstract: Objective The aim of this clinical trial was to investigate semaglutide in combination with fenofibrate in the treatment of patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Methods A total of 102 patients with T2DM and NAFLD were encountered in our hospital between January 2022 and January 2024, and were randomly assigned to receive fenofibrate at base of metformin in 51 cases in control, or receive semaglutide at base of treatment as mentioned in the control in another 51 cases in the observation for six months. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hPBG) and Hemoglobin A1c (HbA1c) levels were routinely detected, and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were assayed by ELISA. Visceral and subcutaneous fat areas were obtained by special equipment. Results By end of six-month treatment, body mass index, FBG, 2hPBG and HbA1c levels in the observation group were (24.6±2.1)kg/m², (6.0±1.3)mmol/L, (7.0±0.8)mmol/L and (6.3±0.8)%, all significantly lower than [(27.8±5.7)kg/m², (7.8±1.3)mmol/L, (8.5±1.0)mmol/L and (6.9±1.0)%, respectively, P＜0.05] in the control; serum TC, TG and LDL levels were (4.9±0.4)mmol/L, (1.9±0.3)mmol/L and (2.4±0.4)mmol/L, all much lower than [(5.6±0.9)mmol/L, (3.2±0.4)mmol/L and (3.6±0.5)mmol/L, respectively, P＜0.05], while serum HDL level was (1.2±0.5)mmol/L, much higher than [(1.0±0.3)mmol/L, P＜0.05] in the control group; visceral and subcutaneous fat areas were (135.11±14.0)cm² and (202.3±18.4)cm², both significantly lower than [(164.9±18.7)cm² and (240.7±23.3)cm², respectively, P＜0.05], and serum IL-6 and TNF-α levels were (5.7±2.4)pg/mL and (18.9±4.7)pg/mL, both significantly lower than [(19.2±3.0)pg/mL and (46.1±5.5)pg/mL, respectively, P＜0.05] in the control group. Conclusion The regimen with semaglutide, fenofibrate and metformin at base of diet control and exercise in dealing with patients with T2DM and concomitant NAFLD could have a short-term efficacy of weight loss, and needs further clinical investigation.

Key words: Non-alcoholic fatty liver disease, Type 2 diabetes mellitus, Semaglutide, Fenofibrate, Therapy