Impact of Short-term Intensive De-escalation Therapy on Long-term Regimen Simplification

This is a multicenter, randomized, controlled, open-label, clinical superiority trial. The participants will be recruited from 10 centers in China. The enrolled participants will be randomly assigned into 3 groups, designated as Group A , B and C.

Group A (CSII with wearables)：Continuous subcutaneous insulin infusion (CSII) will be applied to the participants for 1-2 weeks and thereafter the combination therapy of basal insulin, metformin and vildagliptin for the next 10 weeks and then insulin will be suspended. The participants are wearing wearables.

Group B (CSII without wearbles): CSII will be applied to the participants for 1-2 weeks and thereafter the combination therapy of basal insulin, metformin and vildagliptin for the next 10 weeks and then insulin will be suspended.

Group C (Basal insulin treatment): The participants will be applied the combination therapy of basal insulin, vildagliptin and metformin for the entire 12 weeks and then insulin will be suspended.

Participants in both Group A, B and Group C will then receive combination therapy of metformin and vildagliptin, and be followed-up at the 16th, 20th, 24th, 28th, 32nd and 36th weeks. The doses of metformin and vildagliptin are set as 1.0~2.0g/d and 100mg/d, respectively. If the participants cannot tolerate metformin, then acarbose (50-100mg tid) or SGLT2 inhibitor can be instead used. If glucose is not well controlled, sulfonylureas or glinides can be added as a rescue treatment.

Inclusion criteria

• Type 2 diabetes diagnosed according to WHO criteria (1999); With a duration of 1~15 years;
• With two or more oral hypoglycemic drugs, or basal insulin and 1-2 oral hypglycemic agents, used for at least 3 months;
• HbA1c of 7.5 to 13% and fasting C-peptide > 0.4 nmol/L;
• Age of 18 to 70 years;
• BMI of 20 to 35 kg/m²；
• Capable of and willing to follow doctors' instructions to:

• Self-monitor blood glucose according to the protocol;

• Follow the protocol and have regular visits as required; ③ Record and maintain the research diary, as required by the protocol; ④ Keep contact with the investigators and receive phone calls during the study.

Exclusion criteria

• Type 1 diabetes or specific types of diabetes;
• Those who have received premixed insulin therapy and/or basal - meal insulin and/or basal insulin-oral hypoglycemic agents treatment accumulation for 7 days or more, and those who have received CSII therapy in the last one year, and those who have received GLP-1 analogue within 3 months before screening;
• Those who have acute diabetic complications (diabetic ketoacidosis, hyperosmotic hyperglycemia coma or lactic acidosis);
• Those who have severe diabetic microvascular complications (proliferative retinopathy, clinical proteinuria, and glomerular filtration rate less than 45 ml/min, uncontrolled diabetic neuropathy and obvious diabetic autonomic neuropathy);
• Those with ALT >2.5 times of the upper limit of normal (ULN), bilirubin > 1.5 times of ULN；
• Those with known macrovascular disease: Patients with acute cerebrovascular accident, acute coronary syndrome, unstable angina, peripheral artery disease who have received vascular intervention or amputation in the 12 months before enrollment; Or chronic cardiac dysfunction with cardiac function grade III or above;
• Those with poor blood pressure control (systolic blood pressure≥160mmHg and/or sitting diastolic blood pressure ≥110mmHg) and inability to control under 160/110mmhg within 1 week;
• Serious systemic disease or malignant tumor, chronic diarrhea, etc；
• Those with drugs that may affect blood glucose for a cumulative time of more than 1 week within 12 weeks, such as oral/venous glucocorticoid, growth hormone, estrogen/ progesterone, high-dose diuretics, antipsychotic drugs. However, low-dose diuretics for antihypertensive purposes (HCTZ < 25mg/d, indapamide < 1.5mg/d) and physiologic dose of thyroid hormone for replacement therapy are not included；
• Any factors that may affect the participation of the subject in the study or the evaluation of the results；
• Pregnancy or planned pregnancy, lactation subjects.