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

NCT ID: NCT02462369

Last Updated: 2015-07-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2017-10-31

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.

Conditions

Microalbuminuria; Microalbuminuria /Creatinine Ratios ACR

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Saxagliptin

Saxagliptin 5mg/d, 52 weeks

Group Type: EXPERIMENTAL

Saxagliptin

Intervention Type: DRUG

glimepiride

glimepiride 1\~4mg/d,52 weeks

Group Type: ACTIVE_COMPARATOR

glimepiride

Intervention Type: DRUG

Interventions

Saxagliptin

Intervention Type: DRUG

glimepiride

Intervention Type: DRUG

Eligibility Criteria

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.

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

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

7. 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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Second Hospital of Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Mosenzon O, Bhatt DL, Likwat L, et al. Effect of saxagliptin on renal outcomes. 2014 ADA poster. 544-P.

Reference Type: BACKGROUND

Parving HH, Lewis JB, Ravid M, Remuzzi G, Hunsicker LG; DEMAND investigators. Prevalence and risk factors for microalbuminuria in a referred cohort of type II diabetic patients: a global perspective. Kidney Int. 2006 Jun;69(11):2057-63. doi: 10.1038/sj.ki.5000377.

Reference Type: RESULT

PMID: 16612330 (View on PubMed)

Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010 Apr 14;303(14):1410-8. doi: 10.1001/jama.2010.405.

Reference Type: RESULT

PMID: 20388897 (View on PubMed)

Hattori S. Sitagliptin reduces albuminuria in patients with type 2 diabetes. Endocr J. 2011;58(1):69-73. doi: 10.1507/endocrj.k10e-382. Epub 2010 Dec 28.

Reference Type: RESULT

PMID: 21206136 (View on PubMed)

Liu WJ, Xie SH, Liu YN, Kim W, Jin HY, Park SK, Shao YM, Park TS. Dipeptidyl peptidase IV inhibitor attenuates kidney injury in streptozotocin-induced diabetic rats. J Pharmacol Exp Ther. 2012 Feb;340(2):248-55. doi: 10.1124/jpet.111.186866. Epub 2011 Oct 24.

Reference Type: RESULT

PMID: 22025647 (View on PubMed)

Groop PH, Cooper ME, Perkovic V, Emser A, Woerle HJ, von Eynatten M. Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction. Diabetes Care. 2013 Nov;36(11):3460-8. doi: 10.2337/dc13-0323. Epub 2013 Sep 11.

Reference Type: RESULT

PMID: 24026560 (View on PubMed)

Other Identifiers

SecondNanjingMU

Identifier Type: -

Identifier Source: org_study_id