Saxagliptin's Effects on Microalbuminuria Improvement in Type 2 Diabetic Patients

Phase 4

• Conditions: Microalbuminuria /Creatinine Ratios ACR; Microalbuminuria
• Interventions: Drug: Saxagliptin; Drug: glimepiride

• Registration Number: NCT02462369
• Lead Sponsor: The Second Hospital of Nanjing Medical University

Brief Summary

This study compare the effects on microalbuminuria improvement in type 2 diabetes mellitus (T2DM) treated with saxagliptin or glimepiride.All patients received metformin and/or acarbose, and randomly receive saxagliptin (5mg/d) or glimepiride (1-4mg/d).

Detailed Description

Both sitagliptin and glimepiride are hypoglycemic agents,but they do so by different mechanisms.sitagliptin can delay degradation of glucagon-like peptide -1 (GLP-1) by inhibit DPPIV to decrease serum glucose level.glimepiride stimulates islets B cell to secrete insulin to decrease serum glucose level.

Preclinical studies and several clinical trials (including vildagliptin, sitagliptin, linagliptin, exenatide) suggested that DPP-4i/GLP-1 might have a potential to lower albuminuria, albumin-creatinine ratio (ACR) or improve glomerular filtration rate(GFR) and the effect might be independent of changes in glucose control. Recently, SAVOR outcomes also showed that saxagliptin might have nephroprotective effects, and the proportion of patients with microalbuminuria converted into normal albuminuria after saxagliptin treatment for 1 year is 31.3%, but the mechanism is still unclear.

Study Timeline

• Status Verified: 2015-04
• Study First Submitted: 2015-04-08
• Study Start: 2015-06
• Study First Submitted QC: 2015-06-01
• Study First Posted: 2015-06-04
• Last Update Submitted: 2015-07-27
• Last Update Posted: 2015-07-28
• Primary Completion: 2017-04
• Study Completion: 2017-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures
2. Diagnosed with type 2 diabetes with stable, doses of metformin (1000mg~2550mg/d) or acarbose (100mg~300mg/d) at least 60 days
3. Men and women (non-pregnant and using a medically approved birth-control method) aged at age ≥20 and ≤70 years at screening
4. HbA1c ≥ 7.0% and ≤ 9.0% at screening
5. 24-hour urinary albumin level of 30-300 mg/24 h

Exclusion Criteria

1．Women, who are pregnant, or 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:

• Type 1 diabetes mellitus, diabetes resulting from pancreatic injury or secondary forms of diabetes, e.g acromegaly or Cushing's syndrome.

• Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within the past 6 months.

  3. Previous treatment with any dipeptidyl peptidase-4 (DPP4) inhibitor or GLP-1 receptor agonists within the past 6 months． 4. History of hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to dipeptidyl peptidase-4 inhibitor (DPP4), glimepiride, metformin or acarbose.

  4. Treatment with systemic glucocorticoids (oral, intravenous) for more than consecutive 7 days within the past 6 months.

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

  6. Patients with clinically apparent liver disease characterized by either one of the following:

• alanine aminotransferase((ALT) or aspartate aminotransferase(AST) > 3x upper limit of normal (ULN) confirmed on two consecutive measurements within 4 weeks prior to screening period

• 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.

• Acute viral or active autoimmune, alcoholic, or other types of hepatitis.

  8. Patients with moderate /severe renal impairment or end-stage renal disease (CrCl ≤ 50 mL/min) at screening or within 4 weeks prior to screening

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

  10. 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.

  11. History of chronic pancreatitis or idiopathic acute pancreatitis.

  12. History of gastrointestinal disease including gastroenterostomy, enterectomy, severe hernia, intestinal obstruction, intestinal ulcer.

  13. History of medullary thyroid carcinoma.

  14. History of alcohol abuse or illegal drug abuse within the past 12 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saxagliptin	Saxagliptin	Saxagliptin 5mg/d, 52 weeks
glimepiride	glimepiride	glimepiride 1\~4mg/d,52 weeks

Primary Outcome Measures

Name	Time	Method
microalbuminuria improvement in T2DM treated with saxagliptin	52 weeks

Secondary Outcome Measures

Name	Time	Method
incidence of hypoglycaemia of saxagliptin or glimepiride	52 weeks