OBJECTIVE: The objective of the present study was to observe the effect of sitagliptin on obese patients with insulin treatment- induced diabetes mellitus. PATIENTS AND METHODS: A total of 120 obese patients with insulin treatment-induced diabetes mellitus were consecutively selected and divided into the control group (n= 35), observation group 1 (n= 40), and observation group 2 (n= 45). The control group received different types or doses of insulin, observation group 1 received insulin combined with metformin, and observation group 2 received insulin combined with sitagliptin. The therapeutic effects were compared at the 6-month follow-up visit. RESULTS: Body mass index (BMI) was lower in observation group 1 and observation group 2, and higher in the control group compared with before treatment; the occurrence of hypoglycemia in observation group 2 was lower than in the other two groups, and the differences were statistically significant (p< 0.05). After treatment, the fasting insulin (FINS) and homeostatic model assessment insulin-resistance (HOMA-IR) in observation group 2 were significantly lower than in the other two groups (p< 0.05). Adiponectin levels were increased and leptin and visfatin levels were decreased in observation group 2 after treatment, and the differences were statistically significant (p< 0.05). The levels of fasting blood glucose, hemoglobin A1c, total cholesterol, triglyceride, and low-density lipoprotein in the three groups were not significantly different (p> 0.05). CONCLUSIONS: Sitagliptin can reduce BMI and the occurrence of hypoglycemia in obese patients with insulin treatment-induced diabetes mellitus, and the effect may be related to decreased HOMA-IR, decreased leptin and visfatin levels, and increased adiponectin levels.