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Background Incretin-based therapies provide additional options for treating type 2 diabetes.We aimed to evaluate the efficacy and tolerability of exenatide monotherapy in obese patients with type 2 diabetes.Methods A 26-week,mefformin controlled,parallel-group study was conducted among antidiabetic drug-naive obese patients aged ＞18 years,and with type 2 diabetes.Participating patients were randomly assigned to receive exenatide or metformin treatments.Results Fifty-nine patients (age (50.5±8.6) years,body mass index (BMI) (30.2±1.6) kg/m2,and hemoglobin A1C (HbA1c (8.2±1.2)％) were enrolled in the study.Glucose control and weight reduction improved in both groups receiving treatment.HbA1c and oral glucose tolerance test (OGTT) 2 hour glycemia reduction with exenatide was superior to that obtained with mefformin ((-2.10±1.79)％ vs.(-1.66±1.38)％,(-5.11±2.68) mmol/L vs.(-2.80±2.70) mmol/L,P ＜0.05).Fast plasma glucose (FPG) reduction was not significantly different between the two groups ((-1.8±2.0) mmol/L vs.(-1.6±1.7) mmol/L,P ＞0.05).Patients treated with exenatide achieved HbA1c of ＜7％ (97％ of patients) and ＜6.5％ (79％)at end-point,vs.93％ and 73％ with metformin (P ＞0.05).Greater weight reduction was also achieved with exenatide ((-5.80±3.66) kg) than with metformin ((-3.81±1.38) kg,P ＜0.01).Homeostasis model assessment of beta-cell function (HOMA-B) was not significantly increased,but the insulinogenic index and HOMA for insulin sensitivity (HOMA-S) were greatly improved in the exenatide group (P ＜0.05).Nausea was the most common adverse effect in exenatide treatment (30％ vs.8％; P ＜0.05),but most cases were of mild to moderate intensity.One case in the exenatide group was withdrawn earlrly because of severe nausea.Hypoglycemia events were often observed during the first 4 weeks,with 12％of patients in the exenatide and 3.2％ in metformin groups,respectively (P ＜0.05).No incidents of severe hypoglycemia were reported.Conclusions Exenatide demonstrated more beneficial effects on HbA1c.weight reduction and insulin resistance during 26 weeks of treatment,but there were more hypoglycemic events and mild-to-moderate nausea compared with metformin.These results suggested that exenatide monotherapy may provide a viable treatment option in newly developed type 2 diabetes.