Objective To investigate the safety and efficacy of polyethylene glycol loxenatide（PEX168） combined with metformin in newly diagnosed obese patients with type 2 diabetes mellitus（T2DM）. Methods Eighty newly diagnosed obese patients with T2DM in the Department of Endocrinology and Metabolism of Xijing Hospital were selected and divided into treatment group（n = 40）and control group（n = 40）by random number table method. The treatment group was given PEX168 0.2 mg once a week combined with metformin 500 mg three times a day，and the control group with metformin 500 mg three times a day. After 12 weeks，fasting blood glucose （FBG），2⁃hour postprandial blood glucose（PBG），glycosylated hemoglobin（HbA1c），fasting insulin（FINS）， body mass index（BMI），blood pressure（SBP/DBP），total cholesterol（TC），triglyceride（TG），high density lipoprotein cholesterol（HDL⁃C），low density lipoprotein cholesterol（LDL⁃C）and uric acid（UA）were observed. The glomerular filtration rate（eGFR），insulin resistance index（HOMA⁃IR）and islet β⁃cell function（HOMA⁃β） were calculated. Adverse reactions in the two groups were observed as well. Results After 12 weeks of treatment， the lever of FBG，PBG，HbA1c，BMI，SBP，DBP，TG，TC，UA，HOMA⁃IR in both groups were lower，espe⁃ cially in the treatment group（P < 0.05）. Significant decrease of LDL⁃C was observed in the treatment group，but not in the control group（P < 0.05）. Although there was no significant difference in HOMA⁃β and eGFR between the two groups after 12 weeks of treatment，both of them were improved from baseline. Conclusion For newly diagnosed obese patientswith T2DM，PEX168 combined with metformin can rapidly and effectively control blood glucose，improve islet cell function，body weight，blood pressure，blood lipids and uric acid，and has significant cardiovascular and renal benefits，without increasing the risk of adverse events.