Effect of Exenatide on 24h-UAER in Patients With Diabetic Nephropathy

Objective:

To evaluate effect of exenatide on 24-UAER in patients with diabetic nephropathy

Hypothesis:

Compared with glargine plus lispro group, at 24 weeks, glargine plus exenatide group can: 1) take more significant reduction of 24h-UAER; 2) take more reduction of ACR; 3) take more weight loss, blood pressure reduction; 4) take lower hypoglycemia incidence and less insulin dosage.

Primary endpoint： The proportion of reduction of 24h-UAER(urinary albumin excretion rates)

Secondary endpoints： 24h-UAER at 24 weeks; the rate of urinary albumin to creatinine ratio(ACR) change at 24 weeks; HbA1c, FPG,PPG, weight , BP

Treatment duration： 24weeks

Patient/Sites： 90 patients / 3 sites

Timeline (best case)： Planed duration of recruitment period: 6 month Planed date for first screening: 1 October 2015 Planed completion of the last subject: 1 March 2017 Planned completion of clinical trial report: 30 October 2017

Inclusion criteria

• Provision of informed consent prior to any study specific procedures.
• Diagnosed with type 2 diabetes with HbA1c ≥ 7.0% and ≤ 11.0% at screening (the result is valid for seven days).
• Men and women (non-pregnant and using a medically approved birth-control method) aged from 18 to 80 at screening.
• Body mass index (BMI) ≥18 and ≤35 kg/m2.
• Blood Pressure (BP) ≥ 90/60mmHg and ≤160/100mmHg.

6.24h urinary albumin excretion rate (UAE) >0.3g/24h after 3 months treatment with several hypoglycemic agents (sulphonylureas, metformin, AG-inhibitor, meglitinides or insulin), ACEI/ARB and salt restriction(the result is valid for seven days).

7.eGFR >30ml/min(the result is valid for seven days).

Exclusion criteria

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.

• Diagnosis or history of:

• Type 1 diabetes mellitus, diabetes resulting from pancreatic injury or secondary forms of diabetes, eg, acromegaly or Cushing's syndrome.
• Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within the past 6 months.

• Previous treatment with any Thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP4) inhibitor or GLP-1 receptor agonists within the past 3 months.

• History of hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to exenatide.

• Blood amylase and/or lipase > 2 times the upper limit of the normal (ULN) laboratory range.

• Hyperkalemia (K+>5.5mmol/L).

• eGFR <30ml/min/1.73m2.

• Patients without diabetic retinopathy.

• Triglycerides (fasting) > 4.5 mmol/L (400 mg/dL) at screening or within 4 weeks prior to screening (by local laboratory).

• Patients with clinically apparent liver disease characterized by ALT or AST > 3ULN confirmed on two consecutive measurements (by local laboratory) within 4 weeks prior to screening period.

• Significant cardiovascular history within the past 3 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.

• Congestive heart failure defined as New York Heart Association (NYHA) class III or IV.

• History of chronic pancreatitis or idiopathic acute pancreatitis.

• History of medullary thyroid carcinoma.