Renoprotective Effects of Dapagliflozin in Type 2 Diabetes

Sponsor
M.H.H. Kramer
Study ID
NCT02682563
Phase
PHASE4
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
35 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Dapagliflozin 10mg QD — DRUG
    Dapagliflozin 10mg once daily for 12 weeks
  • Gliclazide 30mg QD — DRUG
    Gliclazide30mg once daily for 12 weeks

Study Details

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.

Key Dates

Start date
Feb 29, 2016
Status verified
Jul 2020
Primary completion
Sep 30, 2018
Completion
Sep 30, 2018

Study Design

Enrollment
44 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION

Arms

  • Experimental: Dapagliflozin 10mg once daily
    Once daily treatment with oral dapagliflozin (forxiga) 10mg for 12 consecutive weeks.
  • Active Comparator: Gliclazide modified release 30mg once daily
    Once daily treatment with oral gliclazide MR 30mg for 12 consecutive weeks.

Primary Outcome Measure

Glomerular Filtration Rate (GFR) in ml/Min [ Time Frame: 12 weeks ]

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