【Abstract】Objective To investigate the initial insulin treatment plan for patients with diabetes mellitus inadequately controlled with oral antidiabetic drugs and analyze its safety. Methods 126 patients with diabetes mellitus inadequately controlled with metformin were randomized into group A, group B and group C. On the basis of treatment with metformin, group A were treated with sitagliptin, group B with starting dose 10 U/d of insulin and group C with 15 U/d of insulin. According to the blood glucose control during treatment, the dose was adjusted to maintain the fasting blood glucose ≤ 56 mmol/L. The control rates of blood glucose, standard time and incidence of hypoglycemia in the three groups were recorded. The body mass index (BMI) and body weight difference were calculated. The fasting plasma glucose (FPG), postprandial 2h plasma glucose (2hPG), glycosylated hemoglobin (HbA1c), insulin resistance index (HOMAIR), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) in the three groups were statistically analyzed before and after treatment. Results There were 5 cases in group A, 7 cases in group B and 8 cases in group C lost to follow up. There was no significant difference in the control rate of blood glucose and incidence of hypoglycemia among the three groups (P＞0.05). The standard time of group C was shorter than that of group A and group B (P＜0.05) but there was no significant difference between group A and group B (P＞0.05). After treatment, FPG, 2hPG, HbA1c and HOMAIR decreased in the three group while FINS increased (P＜0.05) but there was no significant difference between groups (P＞0.05). BMI and body weight difference of group A were lower than those of group B and group C (P＜0.05) but there was no significant difference between group B and group C (P＞0.05). Conclusion The hypoglycemic effects of sitagliptin and insulin glargine are good in patients with diabetes mellitus inadequately controlled with metformin. High starting dose of insulin glargine can shorten the standard time of blood glucose but sitagliptin has more advantages in controlling weight.