Renohemodynamic Effects of Combined empagliflOzin and LosARtan
Status:
Completed
Trial end date:
2021-09-27
Target enrollment:
Participant gender:
Summary
Worldwide, diabetic kidney disease (DKD) is the most common cause of chronic and end stage
kidney disease. In parallel with the ever-increasing rates of obesity and type 2 diabetes
(T2D), the incidence of DKD is expected to further increase in the coming years. DKD is a
multi-factorial condition, involving pathophysiological factors such as chronic
hyperglycemia, obesity, systemic- and glomerular hypertension, dyslipidemia, oxidative stress
and pro-inflammatory cytokines. Large-sized prospective randomized clinical trials indicate
that intensified glucose and blood pressure control, the latter especially by using agents
that interfere with the renin-angiotensin-aldosterone system (RAS), halts the onset and
(particularly) the progression of DKD, in both type 1 diabetes mellitus (T1DM) and T2DM
patients. However, despite the wide use of angiotensin-converting enzyme (ACE) inhibitors and
angiotensin receptor blockers (ARBs), a considerable amount of patients develop DKD,
indicating an unmet need for renoprotective therapies. Sodium-glucose linked transporters
(SGLT-2) inhibitors are a relatively novel glucose-lowering drug for the treatment of T2DM.
These agents seem to exert pleiotropic actions 'beyond glucose control'. SGLT-2 inhibitors
decrease proximal sodium reabsorption and decrease glomerular pressure and albuminuria in
type 2 diabetes. In addition, SGLT-2 inhibitors reduce blood pressure and body weight. At
this point in time, the renoprotective mechanisms involved with SGLT-2 inhibition still
remain speculative, though a consistent finding is that SGLT-2 inhibitors reduce estimated
eGFR after first dosing, which is reversible after treatment cessation. This "dip" indicates
a renal hemodynamic phenomenon reminiscent of the RAS blockers and is thought to reflect a
reduction in intraglomerular pressure. The potential renoprotective effects and mechanisms of
combination therapy of SGLT-2 inhibitors and RAS inhibitors have not been sufficiently
detailed in human type 2 diabetes. Therefore, the current study aims to explore the
underlying mechanism of the improved renal hemodynamics and mechanistics of mono- and
combination therapy with an SGLT-2 inhibitor and a RAS inhibitor on renal physiology in
metformin and/or SU-treated T2DM patients.