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Renoprotective Effects of Dapagliflozin in Type 2 Diabetes

NCT02682563 · Status: COMPLETED · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 44

Last updated 2020-07-07

Study results available
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Summary

Background:

Worldwide, diabetic nephropathy or Diabetic Kidney Disease (DKD), is the most common cause of chronic and end-stage kidney disease. With the increasing rates of obesity and type 2 diabetes (T2DM), many more patients with DKD may be expected in the coming years. Large-sized prospective randomized clinical trials suggest that intensified glucose and blood pressure control, may halt the progression of DKD, both in type 1 diabetes and T2DM. However, despite the wide use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, a considerable amount of patients develop DKD during the course of diabetes, indicating an unmet need for renoprotective therapies. Sodium-glucose linked transporters (SGLT-2) inhibitors are novel glucose-lowering drugs for the treatment of T2DM. These agents seem to exert pleiotropic actions 'beyond glucose control', including reduction of blood pressure and body weight. In addition, SGLT-2 inhibitors decrease proximal sodium reabsorption and decrease glomerular pressure and albuminuria in rodents and type 1 diabetes patients. In rodents, SGLT-2 inhibitors also improved histopathological abnormalities associated with DKD. To date, the potential renoprotective effects and mechanisms of these agents have not been sufficiently detailed in human type 2 diabetes. The current study aims to explore the clinical effects and mechanistics of SGLT-2 inhibitors on renal physiology and biomarkers in metformin-treated T2DM patients with normal kidney function.

Study Design:

Randomized, double-blind, comparator-controlled, intervention trial

Study Endpoints:

Renal hemodynamics, i.e. measured glomerular filtration rate (GFR, ml/min) and effective renal plasma flow (ERPF, ml/min); 24-hour urinary solute excretion; markers of renal damage ; blood pressure; body anthropometrics; systemic hemodynamic variables (including stroke volume, cardiac output and total peripheral resistance); arterial stiffness will be assessed by applanation tonometry, (SphygmoCor®); insulin sensitivity and beta-cell function.

Expected results:

Treatment with the SGLT-2 inhibitor dapagliflozin, as compared to the sulfonylurea (SU) derivative gliclazide, may confer renoprotection by improving renal hemodynamics, and decreasing blood pressure and body weight in type 2 diabetes.

Conditions

  • Diabetes Mellitus, Type 2
  • Diabetic Nephropathies

Interventions

DRUG

Dapagliflozin 10mg QD

Dapagliflozin 10mg once daily for 12 weeks

DRUG

Gliclazide 30mg QD

Gliclazide30mg once daily for 12 weeks

Sponsors & Collaborators

  • AstraZeneca

    collaborator INDUSTRY

  • M.H.H. Kramer

    lead OTHER

Principal Investigators

  • Mark HH Kramer, MD/PhD · Amsterdam UMC, location VUmc

Study Design

Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Model
PARALLEL

Eligibility

Min Age
35 Years
Max Age
75 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2016-02-29
Primary Completion
2018-09-30
Completion
2018-09-30

Countries

  • Netherlands

Study Locations

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Entities

Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02682563 on ClinicalTrials.gov