Objective: To investigate the efficacy of caglilipzin combined with Liraglutide in the treatment of obese type 2 diabetes mellitus (T2DM) and the effects on glucose metabolism indexes and obesity indexes. Methods: 104 obese T2DM patients admitted to our hospital from July 2021 to October 2023 were selected as the study objects. Patients were divided into control group and observation group by random number table method, with 52 cases in each group. Both groups were given metformin and other basic treatment. On this basis, the control group was given caraglipzin treatment; Observation group was treated with liraglutide on the basis of control group. The clinical efficacy, glucose metabolism [fasting blood glucose (FPG), 2 h postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c)], insulin index [Insulin resistance index (HOMA-IR), β cell function index (HOMA-β)], obesity index (waist circumference, hip circumference, body mass index), disease-related indicators [secreted fried-associated protein 5 (SFRP5), total adiponectin (tAPN), irisin (Ir) isin)] and adverse reactions were analyzed and compared between the two groups. Results: The total effective rate of observation group was significantly higher than that of control group (P<0.05). After treatment, HOMA-IR, FPG, 2 hPG and HbA1c in both groups were significantly decreased compared with before treatment, and HOMA-β was significantly increased compared with before treatment, and the improvement of HOMA-IR, FPG, 2 hPG and HbA1c in the observation group was significantly increased compared with the control group (P<0.05). After treatment, the body mass index, waist circumference and hip circumference of both groups were significantly lower than before treatment, and the body mass index, waist circumference and hip circumference of the observation group were significantly lower than that of the control group (P<0.05). After treatment, serum SFRP5, tAPN and Irisin in both groups were significantly higher than before treatment, and serum SFRP5, tAPN and Irisin in observation group were significantly higher than those in control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Caglilipzin combined with liraglutide in the treatment of obese T2DM can improve the therapeutic effect, improve glucose metabolism, insulin function, reduce body weight and blood sugar level in patients with high safety.