Abstract: Objective The aim of this study was to investigate semaglutide in combination with pioglitazone/metformin in the treatment of patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Methods A retrospective study was performed on the clinical materials in 124 patients with T2DM and NAFLD, who were admitted to our hospital between September 2023 and March 2025, and were randomly assigned to receive oral pioglitazone/ metformin in 60 cases for control, or receive intramuscular injection of semaglutide weekly in another 64 cases for 12 weeks. Serum biochemical, sugar and fat parameters were monitored. Results By end of 12-week treatment, serum aspartate aminotransferase and gamma glutamyl transferase levels in combination-treated group were(43.9±5.5)U/L and (63.8±7.1)U/L, both significantly lower than [(49.8±5.7)U/L and (71.5±6.6)U/L, respectively, P<0.05] in the control group; serum fasting insulin level and homeostasis model assessment of insulin resistance in the combination group were(12.1±2.3)μU/mL and (2.4±0.5), both significantly lower than [(14.2±2.6)μU/mL and (2.9±0.6), respectively, P<0.05] in the control, while there was no significant difference as respect to fasting blood glucose levels in the two groups (P>0.05); serum triglyceride, cholesterol and low-density lipoprotein cholesterol in the combination group were(2.0±0.3)mmol/L, (5.3±1.0)mmol/L and (3.0±0.8)mmol/L, all significantly lower than [(2.5±0.6)mmol/L, (5.6±0.8)mmol/L and (3.4±0.9)mmol/L, respectively, P<0.05] in the control; there was no significant difference as respect to incidence of adverse effects, such as nausea and vomiting, fatigue and hypoglycemia between the two groups(7.8% vs. 1.7%, P>0.05). Conclusion Administration of semaglutide plus pioglitazone/metformin therapy in dealing with patients with T2DM and NAFLD is short-termly efficacious, which might improve liver function tests, blood sugar and fat metabolism, and needs further long-term clinical observation.

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