After the screening period, eligible subjects took the hyperinsulinemic euglycemic clamp test and were then admitted to insulin with dapagliflozin (100mg one day) for 4 weeks. During this timeframe, all patients were instructed to change the insulin pump infusion site and provide one profile of 7-point self-monitored blood glucose every three days. The insulin doses were titrated every day by physicians to achieve the glycemic goal. Participants who failed to attain the glycemic target in three consecutive times or could not afford the side effects of hypoglycemic medications were excluded from this study. On the last day of week 4, a FreeStyle Libre Pro Sensor (FGM system) was inserted to record the glycemic data for up to 14 days. At the end of week 5, all antidiabetic agents were stopped and the hyperinsulinemic euglycemic clamp test was performed again for remaining subjects.

After the screening period, eligible subjects took the hyperinsulinemic euglycemic clamp test and were then admitted to insulin with fixed-dose combination of metformin and pioglitazone (two tablets of 500mg metformin plus 15mg pioglitazone) for 4 weeks. During this timeframe, all patients were instructed to change the insulin pump infusion site and provide one profile of 7-point self-monitored blood glucose every three days. The insulin doses were titrated every day by physicians to achieve the glycemic goal. Participants who failed to attain the glycemic target in three consecutive times or could not afford the side effects of hypoglycemic medications were excluded from this study. On the last day of week 4, a FreeStyle Libre Pro Sensor (FGM system) was inserted to record the glycemic data for up to 14 days. At the end of week 5, all antidiabetic agents were stopped and the hyperinsulinemic euglycemic clamp test was performed again for remaining subjects.