Adult male C57BL/6 mice (Slack Laboratory Animal, Shanghai, China), CD-1 mice (Vital River Laboratory Animal Technology Co., Ltd., Beijing, China), and db/db mice (CAVENS Lab Animal Technology Co., Ltd., Changzhou, China) were housed under controlled temperature conditions and a 12 h light/12 h dark cycle with free access to food and water except where noted. To produce diet-induce obesity, 5-month-old mice were fed with HFD (calorie density: 60% total kilocalories from fat and 20% from carbohydrate; Product number: D12492; research Diets, New Brunswick, USA) and plain water for 6 months. Before treatment, body weight, fasting blood glucose, IPGTT, intraperitoneal insulin tolerance testing (IPITT), and food intake were measured as baseline data. Treatment study was performed by intraperitoneally injecting supaglutide (Yinnuo Pharmaceutical Technology Co. Ltd., 300 μg/kg) twice a week (PBS as control) for 4 weeks. Animal care procedures were approved by the Animal Care and Use Committee of the Fudan University Shanghai Medical College and followed the National Institute of Health guidelines on the care and use of animals.