Objective:To explore the potential impact of liraglutide and semaglutide on reducing homocysteine(Hey)levels in patients with type 2 diabetes mellitus(T2DM).Methods:A total of 108 patients with T2DM were selected and divided into liraglutide group(n=56,all received liraglutide)and semaglutide group(n=52,all received semaglutide)according to different treatment meth-ods,both treated continuously for 12 weeks.The levels of glucose and lipid metabolism indicators,serum Hey levels,inflammatory factor levels,incidence of adverse reactions,and cost-effectiveness of treatment were compared between the two groups.Results:After 4 and 12 weeks of treatment,the levels of fasting plasma glucose(FPG),2-hour postprandial plasma glucose(2 hPG),glycosylated hemoglobin(HbA1c),homocysteine(Hey),ApoA1/ApoB,and C-reactive protein(CRP)in both groups exhibited a decrease compared to pre-treatment levels.Additionally,the level of 25-hydroxyvitamin D[25(OH)D]showed a notable increase after treatment initiation(P＜0.05).After 12 weeks of treatment,the FPG,2 hPG,HbA1c,and Hcy levels in liraglutide group were lower compared to those observed after only 4 weeks of treatment.Moreover,their level of 25(OH)D was higher than that seen after 4 weeks of treatment(P＜0.05).There were no statistically significant differences between the two groups regarding FPG,2 hPG,HbA1c,Hcy,ApoA1/ApoB CRP or 25(OH)D levels following 4 weeks of treatment(P＞0.05).However,after completing a full course of twelve-weeks'therapy with sema-glutide or liraglutide respectively,the semaglutide group displayed higher FPG,2 hPG,Hb AIC,and HCy values when compared to the liraglutide group.Furthermore,the levelof vitamin D(25-OHD3)was lower in patients treated with semagluti decomparedtothose treated with liraglutide(P＜0.05).There was no statistically significant difference in terms o f adverse reactions incidence between these two groups(P＞0.05).The cost-effectiveness analysis revealed that liraglutide was more economical than semaglutide.Conclusion:In the initial phase of T2DM,liraglutide and semaglutide demonstrate effective enhancement in glucose and lipid metabolism while reducing in-flammatory factors and Hcy levels.Their clinical effects are comparable.However,with prolonged treatment duration,liraglutide showed better improvement in glucose and lipid metabolism,inflammatory factors,and Hcy compared to semaglutide,and had higher economic benefits.