Abstract: Objective To determine whether semaglutide (Sema) and empagliflozin  (Empa) can improve aortic injury in obese mice and to compare the efficacy of the two drugs. 
Methods Obese mouse models were constructed by high-fat diet. The obese mice were intervened with Sema, Empa and the combination of Sema and Empa (S+E), respectively. The mice were closely monitored for changes in body weight. Serological parameters and changes in aortic function and structure were measured at the end of the experiment. 
Results Under the influence of a high-fat diet, the weight of mice in each group increased significantly, while the weight of mice in each group subjected to different drug interventions decreased. Statistical analysis showed that there were significant differences in the interaction between groups, time points, and time points between groups (P＜0.05). Specifically, total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) of mice in the high-fat diet (HFD group) were significantly higher than those of the normal control diet (NCD group) (P＜0.001). In addition, after glucose load, the glucose of the mice in the HFD group was higher than that of the NCD group at all time points. In the mean time, the pulse wave velocity, aortic intima-media thickness(IMT) and collagen content of the mice in the HFD group were also significantly higher than those in the NCD group, showing significant differences (P＜0.05). Compared with the HFD group, the TG level of mice receiving Sema intervention and S+E intervention was significantly reduced (P＜0.05). In addition, the Sema group, Empa group and S+E group also showed significant results in reducing the levels of TC and LDL-C (P＜0.05). However, the difference in high-density lipoprotein cholesterol (HDL-C) levels between drug intervention groups was not significant. In terms of blood glucose levels, compared with the NCD group, the fasting blood glucose levels of mice in the Sema group, Empa group and S+E group increased, but the blood glucose level of these groups decreased significantly at 15 min and 30 min after glucose load (P＜0.05). In terms of pulse wave velocity, the pulse wave velocity of the mice in the Sema group, Empa group and S+E group was lower than that of the HFD group, whereas the pulse wave velocity of the mice in the Empa group was higher than that of the Sema group and the S+E group, suggesting significant difference (P＜0.05). In terms of the elastic fiber area of the aorta, no significant difference was observed between the NCD group, the HFD group, the Sema group, the Empa group and the S+E group (P＞0.05). However, in terms of the aortic IMT and collagen content, the values of the Sema group and the S+E group mice were significantly lower than those of the HFD group, showing significant differences (P＜0.05). 
Conclusion Our results suggest that both Sema and Empa have a protective effect against obesity-induced structural and functional impairment of the aorta. 

Key words: obesity, semaglutide, empagliflozin