Renoprotective Effects of Dapagliflozin in Type 2 Diabetes
Status:
Completed
Trial end date:
2018-09-01
Target enrollment:
Participant gender:
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.