Abstract: Objective This study aimed to explore exenatide in combination with metformin in treatment of patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) and its impact on blood lipid metabolism, and high mobility group protein B1 (HMGB1) and adiponectin (APN) levels. Methods A total of 156 patients with NAFLD and T2DM were enrolled in our hospital between January 2022 and December 2024, and were randomly divided into control (n=78) and observation (n=78), receiving metformin or exenatide and metformin combination therapy for six months. Fasting insulin level was detected by radioimmunoassay, and serum HMGB1 and APN levels were assayed by ELISA. Results By end of 24-week treatment, fasting insulin and fasting blood glucose levels in the combination group were(7.3±1.1)μU/ml and (5.6±0.7)mmol/L, both much lower than [(8.9±1.8)μU/ml and (6.5±0.8)mmol/L, respectively, P＜0.05] in the metformin-treated patients; serum ALT and AST levels were (45.7±7.4)U/L and (34.9±5.8)U/L, both significantly lower than [(59.6±8.2)U/L and (67.1±6.4)U/L, respectively, P＜0.05] in the metformin-treated patients; serum triglyceride, total cholesterol and low-density lipoprotein cholesterol levels were (1.7±0.5)mmol/L, (5.2±0.6)mmol/L and (2.5±0.6)mmol/L, all much lower than [(3.6±0.4)mmol/L, (5.9±0.7)mmol/L and (3.1±0.7)mmol/L, respectively, P＜0.05], while serum high-density lipoprotein cholesterol level was (1.1±0.3)mmol/L, much higher than [(0.9±0.2)mmol/L, P＜0.05] in the metformin-treated patients; serum HMGB1 level was (4.7±0.9)ng/mL, much lower than [(6.8±1.3)ng/mL, P＜0.05], while serum APN level was (14.8±2.7)mg/L, much higher than [(8.5±2.4)mg/L,P＜0.05] in the metformin-treated patients. Conclusion Exenatide in combination with metformin in dealing with patients with NAFLD and T2DM could improve glucose and lipid metabolism, promote the recovery of liver function tests, which might be related to the regulation of HMGB1 and APN.

Key words: Non-alcoholic fatty liver disease, Type 2 diabetes mellitus, Metformin, Exenatide, High mobility group protein B1, Adiponectin, Therapy