Type 2 diabetes is a major risk factor
for macrovascular and microvascular disease.
1 Kidney disease develops in approximately
35% of patients with type 2 diabetes2 and
is associated with increased mortality.3 Intensive
glucose-lowering strategies have been shown to
reduce surrogate markers of renal complications
in patients with type 2 diabetes; however, evidence
for improvement in advanced renal complications
is limited.4-8 Thus, despite optimized
glucose control and the use of single-agent
blockade of the renin–angiotensin–aldosterone
system (RAAS), patients with type 2 diabetes
remain at increased risk for death and complications
from cardiorenal causes.9,10
Empagliflozin, a selective sodium–glucose cotransporter
2 inhibitor, reduces hyperglycemia
in patients with type 2 diabetes by reducing the
renal reabsorption of glucose, thereby increasing
urinary glucose excretion.11 The use of empagliflozin
has been associated with a lowering of
glycated hemoglobin levels in patients with
type 2 diabetes, including those with stage 2 or
3a chronic kidney disease, and with reductions
in weight and blood pressure, without increases
in heart rate.12-19 Empagliflozin has been shown
to reduce intraglomerular pressure and improve
hyperfiltration in patients with type 1 diabetes,20,21
and it has been suggested that these effects may
translate into improved renal outcomes.22 However,
concern has been raised that sodium–glucose
cotransporter 2 inhibitors may be associated
with long-term adverse renal effects.
In the recent EMPA-REG OUTCOME trial,23
the primary goal was to assess cardiovascular
outcomes. Here we report the results of a prespecified
secondary objective of that trial, which
was to examine the effects of empagliflozin on
microvascular outcomes and, in particular, progression
of kidney disease in patients with type
2 diabetes at high risk for cardiovascular events.