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2016 ; 4
(20
): 409
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Cardio-renal protection with empagliflozin
#MMPMID27867961
MacIsaac RJ
; Jerums G
; Ekinci EI
Ann Transl Med
2016[Oct]; 4
(20
): 409
PMID27867961
show ga
Cardiovascular (CV) and kidney disease are common and significant complications
in people with type 2 diabetes (T2DM). CV disease is the leading cause of death,
morbidly and hospitalisations for people with T2DM. Furthermore, diabetic kidney
disease is a major risk factor for CV disease and is the main reason why patients
need renal replacement therapy. In this perspective, we highlight the results of
the recent landmark EMPA-REG OUTCOME trial which has shown that empagliflozin, a
member of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor class of glucose
lowering medications, reduces death from CV causes, hospitalisation for heart
failure and progression to end stage kidney disease in patients with T2DM and
established CV disease. The SGLT2 receptor mediates high-capacity glucose uptake
in the early proximal tubule, and SGLT2 inhibitors, via their ability to promote
glycosuria, have been developed as glucose lowering medications. As well as
having a glucose lowering effect, SGLT-2 inhibitors also reduce blood pressure,
promote weight loss and reduce uric acid levels. Potential side-effects or
concerns related to the use of SGLT-2 inhibitors include increased rates of
urinary tract infections, genital tract infections, postural hypotension,
diabetic ketoacidosis, acute kidney injury and possible increased rates of
fractures. The exact mechanisms that result in empagliflozin's dramatic CV and
renal protective effects, with a very favourable safety/tolerability profile, in
the EMPA-REG study remain to be fully defined. However, they are most likely
distinct from the glucose lowering effects of empagliflozin. CV safety trials
involving dapagliflozin and canagliflozin, members of the SGLT-2 class, are under
way and the results from these studies will help to answer the question as to
whether the cardio-renal benefits of empagliflozin are a class-effect or not.
Without doubt, trials to investigate whether SGLT-2 inhibitors have cardio-renal
protective effects in patients without diabetes will start soon.
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