Type 2 diabetes mellitus
Conditions
Interventions
1:saxagliptin combination therapy with metformin
2:saxagliptin combination therapy with acarbose
3:saxagliptin combination therapy with gliclazide MR
Sponsors
China-Japan Friendship Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: For inclusion in the study subjects should fulfil the following criteria: 1. Provision of informed consent prior to any study specific procedures; 2. Diagnosed with type 2 diabetes according to World Health Organization (WHO) 1999 criteria with drug-nave; 3. Men and women (non-pregnant and using a medically approved birth-control method) to be aged from 18 to 80 years old at screening stage; 4. HbA1c more than 8.0% and less than 11.0% at screening (by local laboratory) and HbA1c more than 8.0% and less than 11.0% at pre-randomization visit (by central laboratory); 5. BMI more than 19 and less than 40 kg/m2 at screening stage.
Exclusion criteria
Exclusion criteria: Subjects should not enter the study if any of the following exclusion criteria are fulfilled: 1.Women who are pregnant, intending to become pregnant during the study period, currently lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods; 2. Diagnosis or history of: (1) Type 1 diabetes mellitus, diabetes resulting from pancreatic injury or secondary forms of diabetes, eg, acromegaly or Cushing's syndrome; (2) Acute metabolic diabetic complications such as ketoacidosis or diabetic nonketotic hyperosmolarcoma within the past 6 months. 3. Previous treatment with any dipeptidyl peptidase-4 inhibitor (DPP-4i) or GLP-1 receptor agonists; 4. History of hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to DPP-4i or acarbose, or gliclazide MR, or metformine; 5. Currently use of weight-loss drugs within 3 months at screening; 6. Treatment with systemic glucocorticoids (oral, intravenous) for more than consecutive 7 days within the past 6 months; 7. Treatment with strong cytochrome P450 3A4/5 (CYP450 3A4/5) inhibitors, e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin 8. Triglycerides (fasting) more than 4.5 mmol/L (more than 400 mg/dL) at screening stage; 9. Patients with clinically apparent liver disease characterized by either one of the following: (1) ALT or AST more than 2.5* upper limit of normal (ULN) at screening; (2) Impaired excretory (eg, hyperbilirubinemia) and/or synthetic function, or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites and bleeding from oesophageal varices; (3) Acute viral or active autoimmune, alcoholic, or other types of hepatitis. 10. Patients with impaired kidney function, with serum creatinine more than 133 umol/L for men or more than 124 umol/L for women at screening; 11. History of congestive heart failure defined as New York Heart Association (NYHA) class III or IV; 12. Significant cardiovascular history within the previous 6 months prior to screening defined as: myocardial infarction, coronary angioplasty or bypass graft(s), valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident; 13. History of chronic pancreatitis or idiopathic acute pancreatitis; 14. History of gastrointestinal disease including gastroenterostomy, enterectomy, roemheld syndrome, severe hernia, intestinal obstruction, intestinal ulcer; 15. History of genetic galactose lntolerance, lapp lactase deficiency and glucose-galactose malabsorption; 16. History of medullary thyroid carcinoma; 17. Diagnosed and/or treated malignancy (except for basal cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer) within the past 5 years; 18. History of organ transplant or acquired immunodeficiency syndrome (AIDS); 19. History of alcohol abuse or illegal drug abuse within the past 12 months; 20. Potentially unreliable patients and those judged by the investigator to be unsuitable for the study; 21. Clinically significant hemaologic, renal disease; 22. Family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2; 23. Uncontrolled hypertension (SBP higher than 160 mmHg and /or DBP higher than 100 mmHg); 24. History of laser treatment for proliferative retinopathy with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Absolute change in HbA1c levels from baseline to week 24; | — |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of patients reaching HbA1c less than 7.0% and less than 6.5% at 24 weeks;Changes in FPG, 2h PPG at 24 weeks;Beta cell function and insulin sensitivity (HOMA-?,HOMA-IR, early insulin secretion index, whole body insulin sensitivity index);Change of insulin, glucagon, GIP and GLP-1 level at 24 weeks;Mean AUC of insulin, glucagon, GLP-1 and GIP (Standard meal test) at 24 weeks;Change of fasting lipid profile (TC, LDL-C, HDL-C, TG) at 24 weeks;Change of body weight at 24 weeks;Change of blood pressure (systolic and diastolic); | — |
Countries
China
Contacts
Public ContactYang Wenying
Outcome results
None listed