NCT02682563: RED

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

Completed Phase 4 Results posted Last updated 6 July 2020

What this trial tests

Phase 4 trial testing Dapagliflozin 10mg QD in Diabetes Mellitus, Type 2 in 44 participants. Completed in 1 September 2018.

Timeline

1 February 2016

Primary endpoint
1 September 2018

1 September 2018

Quick facts

Lead sponsor	M.H.H. Kramer
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	44
Start date	1 February 2016
Primary completion	1 September 2018
Estimated completion	1 September 2018
Sites	1 location across Netherlands

Drugs / interventions tested

• Dapagliflozin 10mg QD — full drug profile →
• Gliclazide 30mg QD — full drug profile →

Conditions studied

• Diabetes Mellitus, Type 2 — all drugs for Diabetes Mellitus, Type 2 →
• Diabetic Nephropathies — all drugs for Diabetic Nephropathies →

Sponsor

M.H.H. Kramer — full company profile →

Who can join

Adults 35 to 75, any sex, with Diabetes Mellitus, Type 2 or Diabetic Nephropathies. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy.
   Rayego-Mateos S, Morgado-Pascual JL, Opazo-Ríos L, Guerrero-Hue M, et al · · 2020 · cited 237× · PMID 32471207 · DOI 10.3390/ijms21113798
2. SGLT2 Inhibition and Uric Acid Excretion in Patients with Type 2 Diabetes and Normal Kidney Function.
   Suijk DLS, van Baar MJB, van Bommel EJM, Iqbal Z, et al · · 2022 · cited 76× · PMID 35322793 · DOI 10.2215/cjn.11480821
3. Effects of dapagliflozin and gliclazide on the cardiorenal axis in people with type 2 diabetes.
   van Bommel EJM, Smits MM, Ruiter D, Muskiet MHA, et al · · 2020 · cited 23× · PMID 32516291 · DOI 10.1097/hjh.0000000000002480
4. Insulin Sensitivity and Renal Hemodynamic Function in Metformin-Treated Adults With Type 2 Diabetes and Preserved Renal Function.
   van Bommel EJM, Ruiter D, Muskiet MHA, van Baar MJB, et al · · 2020 · cited 16× · PMID 31662305 · DOI 10.2337/dc19-1651
5. Role of sodium-glucose cotransporter 2 inhibition to mitigate diabetic kidney disease risk in type 1 diabetes.
   van Raalte DH, Bjornstad P. · · 2020 · cited 12× · PMID 32003832 · DOI 10.1093/ndt/gfz228
6. Sodium glucose co-transporter 2 inhibition: a new avenue to protect the kidney.
   Heerspink HJL. · · 2019 · cited 10× · PMID 30789206 · DOI 10.1093/ndt/gfz033
7. The establishment and validation of novel therapeutic targets to retard progression of chronic kidney disease.
   Pollock C, Zuk A, Anders HJ, Ganji MR, et al · · 2017 · cited 4× · PMID 30675427 · DOI 10.1016/j.kisu.2017.07.008
8. Skin microvascular function and renal hemodynamics in overweight patients with type 2 diabetes: A cross-sectional study.
   Bouman EJ, Smits MM, van Bommel EJ, Muskiet MHA, et al · · 2021 · cited 3× · PMID 33864418 · DOI 10.1111/micc.12700