Renoprotective Effects of Dapagliflozin in Type 2 Diabetes (RED)
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|ClinicalTrials.gov Identifier: NCT02682563|
Recruitment Status : Completed
First Posted : February 15, 2016
Results First Posted : July 7, 2020
Last Update Posted : July 7, 2020
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.
Randomized, double-blind, comparator-controlled, intervention trial
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.
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.
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus, Type 2 Diabetic Nephropathies||Drug: Dapagliflozin 10mg QD Drug: Gliclazide 30mg QD||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||44 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double-blind, Comparator-controlled Trial to Assess the Effect of 12-week Treatment With Dapagliflozin Versus Gliclazide on Renal Physiology and Biomarkers in Metformin-treated Patients With Type 2 Diabetes Mellitus|
|Study Start Date :||February 2016|
|Actual Primary Completion Date :||September 2018|
|Actual Study Completion Date :||September 2018|
Experimental: Dapagliflozin 10mg once daily
Once daily treatment with oral dapagliflozin (forxiga) 10mg for 12 consecutive weeks.
Drug: Dapagliflozin 10mg QD
Dapagliflozin 10mg once daily for 12 weeks
Other Name: forxiga
Active Comparator: Gliclazide modified release 30mg once daily
Once daily treatment with oral gliclazide MR 30mg for 12 consecutive weeks.
Drug: Gliclazide 30mg QD
Gliclazide30mg once daily for 12 weeks
Other Name: Diamicron
- Glomerular Filtration Rate (GFR) in ml/Min [ Time Frame: 12 weeks ]Calculated from urinary and plasma inulin concentrations, GFR in ml/min
- Effective Renal Plasma Flow (ERPF) in ml/Min [ Time Frame: 12 weeks ]Calculated from urinary and plasma para-aminohippurate concentrations, ERPF in ml/min
- Fractional Excretion of Sodium in % of Filtered Sodium [ Time Frame: 12 weeks ]Calculated fractional excretions with measured GFR (see above) and urinary and plasma concentrations of sodium. Fractional excretion in % of filtered sodium
- Fractional Excretion of Potassium in % of Filtered Potassium [ Time Frame: 12 weeks ]Calculated fractional excretions with measured GFR (see above) and urinary and plasma concentrations of potassium. Fractional excretion in % of filtered potassium
- Fractional Excretion of Glucose in % of Filtered Glucose [ Time Frame: 12 weeks ]Calculated fractional excretions with measured GFR (see above) and urinary and plasma concentrations of glucose. Fractional excretion in % of filtered glucose
- Urinary Albumin-Creatinine Ratio in mg/mmol [ Time Frame: 12 weeks ]Calculated from measured urinary albumin and creatinin concentrations, in mg/mmol
- Neutrophil Gelatinase-associated Lipocalin (NGAL) [ Time Frame: 12 weeks ]NGAL (ng/mmoll) measured in urine as a marker of renal damage
- Kidney Injury Molecule-1 (KIM-1) in ng/mmol [ Time Frame: 12 weeks ]KIM-1 (ng/mmol) measured in urine as a marker of renal damage
- Body Weight [ Time Frame: 12 weeks ]Measured in kilograms
- Systolic Blood Pressure [ Time Frame: 12 weeks ]Blood pressure will be measured using an automated oscillometric blood pressure device (Dinamap®) in mmHg
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02682563
|VU University Medical Center|
|Amsterdam, Noord-Holland, Netherlands, 1081 HV|
|Principal Investigator:||Mark HH Kramer, MD/PhD||VU University Medical Center|