AIM: To observe the efficacy and safety of two regimens, namely, hengglinide combined with metformin and pioglitazone combined with metformin, in treating patients with type 2 diabetes mellitus (T2DM) complicated with metabolic fatty liver disease (MAFLD). METHODS: Patients with T2DM complicated with MAFLD were randomly divided into experimental group (44 cases) and control group (43 cases). The experimental group was given oral hengglinide tablets (10 mg once a day) combined with metformin (500 mg twice a day), while the control group was given pioglitazone (15 mg twice a day) combined with metformin (500 mg twice a day). The observation period was 12 weeks. Glucose and lipid metabolism, Body mass index (BMI), waist-hip ratio (WHR), waist hip ratio (Whtr), liver function and liver hardness (1iver stiffness measurement, LSM), controlled attenuation index (CAP) and other indicators were compared, and the above data were compared between the two groups after treatment, and the incidence of adverse drug reactions was observed.RESULTS: (1) The BMI of the experimental group and the control group decreased after treatment, but the decrease in the experimental group was greater. The WHR of the experimental group and the control group decreased compared with that before treatment, and the amplitude of the experimental group was greater. The waist height in the experimental group decreased significantly compared with that before treatment, but there was no significant change in the control group.(2) Fasting glucose (FPG), HbA1-glycosylated hemoglobin (HbAlc) and insulin resistance index of steady-state model (HOMA-IR) in the experimental group and the control group all decreased after treatment, but the decrease in the experimental group was even greater. (3) Total cholesterol (TC) and Triglyceride (TG) in the experimental group and the control group decreased after treatment, but there was no statistical difference between the two groups after treatment. Low density lipoprotein cholesterol (LDL-C) in the experimental group and the control group decreased after treatment, especially in the experimental group. High density lipoprotein cholesterol (HDL-C) in the experimental group increased after treatment, and the difference was statistically significant, while there was no difference in the control group before and after treatment. (4) Alanine transaminase (ALT), aspartate aminotransferase (AST) and Gamma-glutamyltransferase (GGT) in the experimental group and the control group all decreased after treatment, especially in the experimental group. LSM and CAP in the experimental group and the control group decreased after treatment, especially in the experimental group. (5) The total incidence of adverse drug reactions was 34.09% (15 cases /44 cases) in the experimental group and 13.95% (6 cases /43 cases) in the control group (all P<0.05). CONCLUSION: Compared with pioglitazone combined with metformin, hengglinide combined with metformin has better effects on glucose and lipid metabolism, obesity, liver function and liver hardness in patients with T2DM complicated with MAFLD, it may be a more comprehensive treatment choice for T2DM complicated with MAFLD.