Objective To explore the hypoglycemic effect of metformin hydrochloride combined with sitagliptin phosphate and its influences on islet function in patients with type 2 diabetes mellitus (T2DM). Methods A total of 94 patients with T2DM treated in the hospital were enrolled from March 2020 to March 2023, and they were randomly divided into control group (47 cases, sitagliptin phosphate) and observation group (47 cases, metformin hydrochloride combined with sitagliptin phosphate). All were continuously treated for 3 months. The blood glucose indexes, blood glucose control, blood lipid indexes, fasting insulin (FINS), insulin resistance index (HOMA-IR), islet C-peptide and adverse reactions were compared between the two groups before and after treatment. Results After treatment, levels of serum glycosylated hemoglobin (HbA1c), the fasting blood glucose (FBG) and 2h postprandial blood glucose (2hPG) in observation group were significantly lower than those in control group (P＜0.05), 24h glucose attainment time in range(TIR) was significantly higher than control group (P＜0.05). The proportions of FPG ＜7.0 mmol and HbA1c ＜6.5% in observation group were significantly higher than those in control group (P＜0.05). The levels of triacylglycerol (TG), cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in observation group were lower than those in control group, while high density lipoprotein cholesterol (HDL-C) was higher than that in control group (P＜0.05). The levels of FINS and islet C-peptide in observation group were higher than those in control group, while HOMA-IR was lower than that in control group (P＜0.05). The level of miR-147 in observation group was higher than that in the control, while the level of miR-96 was lower than that in the control(P＜0.05). There was no significant difference in adverse reactions between the two groups (P＞0.05). Conclusion Metformin hydrochloride combined with sitagliptin phosphate can significantly improve curative effect, lower blood glucose, regulate blood lipid and improve islet function in T2DM patients