Abstract: Objective The aim of this study was to investigate clinical efficacy of semaglutide and metformin combination in treatment of patients with type 2 diabetes mellitus (T2DM) and concomitant nonalcoholic steatohepatitis (NASH). Methods Eighty patients with T2DM and NASH were encountered in our hospital between October 2022 and October 2023, and were randomly assigned to receive metformin in control or to receive metformin with combination of semaglutide subcutaneously in observation group for 24 weeks. Liver biopsies at presentation and at end of 24 week treatment were performed, and liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were detected by Fibroscan 502. Results By end of 24-week treatment, body mass index (BMI), fasting blood glucose (FPG), 2-hour postprandial blood glucose (2hPG), hemoglobin A1c (HbAlc) and insulin resistance index (HOMA-IR)) in observation group were (23.9±0.7)kg/m², (5.5±0.5)mmol/L, (6.5±1.2)mmol/ L, (6.3±0.7)% and (3.6±0.5), all significantly lower than [(25.6±0.8)kg/m², (6.0±0.7)mmol/L, (7.9±1.0)mmol/L, (7.5±0.8)% and (4.7±0.7), respectively P<0.05] in the control; serum triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were(2.7±0.7)mmol/L,(5.1±1.0)mmol/L and (3.3±0.5)mmol/L, all much lower than [(3.4±0.8)mmol/L, (5.8±1.1)mmol/L and (3.7±0.6)mmol/L, respectively, P<0.05], while serum high-density lipoprotein cholesterol (HDL-C)) level was (1.3±0.2)mmol/L, much higher than [(1.1±0.2)mmol/L, P<0.05] in the control; serum liver function tests in the observation group improved greatly (P<0.05); LSM and CAP were (8.6±1.0)kPa and (251.0±18.5)db/m, both much lower than [(10.1±0.9)kPa and (273.0±19.1)db/m, respectively, P<0.05] in the control; liver histo-pathological examination showed that NASH activity score (NAS) improved in 72.5%, much higher than 25.0% in the control group. Conclusion The combination of semaglutide and metformin in treatment of patients with T2DM and NASH is efficacious short-termly, which might modulate blood sugar and lipid metabolism, and improve liver function tests.

Key words: Non-alcoholic steatohepatitis, Type 2 diabetes mellitus, Semaglutide, Metformin, Therapy