The study evaluated the effect of semaglutide treatment for type 2 diabetes mellitus (T2DM), specifically examining its effect on C-peptide levels. A total of 80 patients hospitalized for T2DM were included (January 2022-December 2023), and all patients had conventional treatment with oral metformin. Patients in the control group received subcutaneous insulin aspart, while patients in the observation group received subcutaneous semaglutide. Key variables, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2h-PBG), and time to target blood glucose, were assessed at the baseline and again after three months. Serum endothelin-1 (ET-1), functional vasodilation (FMD), fasting C-peptide, fasting insulin (FINS), and the insulin resistance index (Homa-IR) were also measured. At the end of three months, the observation group had significantly lower 2h-PBG (9.01±0.53 mmol/L) and FBG (6.13±0.68 mmol/L) than the control group (P<0.05). Additionally, the time to target glucose was shorter in the observation group (3.88±0.69 vs. 5.73±1.01 days, P<0.05). The observation group also had lower ET-1, higher FMD, and increased Homa-IR (P<0.05). In conclusion, semaglutide optimizes glycemic control, lowers insulin resistance, and increases vasorelaxation function. Semaglutide has great potential as a therapeutic agent in T2DM.