Chester County Medicine Spring 2021 - 11

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The findings of the DAPA-HF
study welcomed yet another surprise.
Dapagliflozin proved to not only prevent
heart failure in Type 2 diabetics, but to also
be useful as a treatment for heart failure in
diabetics and non-diabetics.

3 MAJOR SURPRISES FOUND WITH
THE SGLT2i

Surprise 1: The SGLT2i Manages
Cardiac and Renal Dysfunction
of Patients with Type 2 Diabetes
Mellitus!
In 2015 a landmark study called
Empagliflozin, Cardiovascular Outcomes,
and Mortality in Type 2 Diabetes (EMPAREG OUTCOME) by Zinman B et al.
was published. The study showed that
patients with Type 2 Diabetes who received
empagliflozin had a lowered mortality
rate due to a reduction in major adverse
cardiovascular events. Specifically, this
group had a decreased rate of non-fatal
heart attack, non-fatal stroke, and lowered
hospitalizations due to heart failure.

Figure 9: Empagliflozin significantly
reduces death from cardiovascular causes
and hospitalizations for heart failure
(EMPA-REG OUTCOME)
In 2017 and 2019, canagliflozin
and dapagliflozin were the focus of
similar trials named Canagliflozin and
Cardiovascular and Renal Events in Type
2 Diabetes (CANVAS) and Dapagliflozin
and Cardiovascular Outcomes in Type
2 Diabetes (DECLARE-TIMI 58). As
seen with empagliflozin, the two other
derivatives showed promising outcomes:
both providing lowered incidence of heart
attack, stroke, hospitalizations due to heart
failure, and death due to cardiovascular
events.

Figure 10: Dapagliflozin significantly
reduces cardiovascular death or
hospitalization for heart failure
(DECLARE-TIMI 58)
The EMPA-REG OUTCOME,
CANVAS, and DECLARE-TIMI 58
studies show that the entire SGLT2i
family not only improves renal functions
of Type 2 Diabetics, but also improves
cardiovascular issues and outcomes.

Figure 11: Dapagliflozin, canagliflozin,
and empagliflozin significantly reduce
cardiovascular death or hospitalization for
heart failure

Surprise 2: The SGLT2i Improves
Management of Heart Failure due
to Reduced Ejection Fraction in
Patients with and without Type 2
Diabetes Mellitus!
As the cardiovascular benefits of the
SGLT2i were unearthed, there came
an increasing motivation to explore the
nuances of this drug class. In 2019,
Dapagliflozin in Patients with Heart Failure
and Reduced Ejection Fraction (DAPAHF) was published. Ejection fraction is the
percentage of blood that is pumped out by
the heart, an important metric conveying
the heart's efficiency.

Figure 12: Dapagliflozin prevents heart
failure in both Diabetics and non-Diabetics
(DAPA-HF)
A similar study, Cardiovascular and
Renal Outcomes with Empagliflozin in
Heart Failure (EMPEROR-Reduced),
was published the following year and the
findings paralleled that of the dapagliflozin
trial: those treated with empagliflozin
had lower rates of cardiovascular death
or hospitalization due to heart failure,
regardless if diabetes was present in the
patient.
The non-discriminatory nature of
dapagliflozin and empagliflozin allows for
their potential usefulness as a cardiovascular
therapy, broadening the scope of the
SGLT2i drug class beyond just diabetes.

Surprise 3: The SGLT2i Protects
the Kidneys of both Diabetic
and Nondiabetic Patients with
Chronic Kidney Disease!
Due to the close relationship between
the cardiovascular system and the kidneys,
patients with chronic kidney disease have
a high incidence of adverse cardiovascular
and renal events.
Following suit of its predecessor
studies, a study published in 2020 called
Dapagliflozin in Patients with chronic
kidney disease (DAPA-CKD) sought to
uncover more about dapagliflozin.
This time, the investigation was
observed through the lens of chronic
kidney disease.
continued on next page >

SPRING 2021 | CHESTER COUNT Y Medicine 11
http://www.chestercms.org
Chester County Medicine Spring 2021

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