Chester County Medicine Spring 2021 - 12

w w w.c h e s t e r c m s .o r g

The SGLT2i: Teaching Us to Know Diabetes by Heart
continued from page 11

Figure 13: A patient with Chronic Kidney
Disease
	 700 million individuals worldwide
have Chronic Kidney Disease. This disease
causes the gradual loss of kidney function
over time and its risk factors include
diabetes, high blood pressure, and heart
disease.
	 The DAPA-CKD study administered
dapagliflozin to a patient population, with
and without diabetes, diagnosed with
Chronic Kidney Disease. This resulted in
significant reduction in the risk of kidney
failure, the risk of cardiovascular death or
hospitalization due to heart failure, and
overall prolonged survival of patients.

Heart: the SGLT2i Reduces
Cardiac Preload and Afterload

Neurohormonal: The SGLT2i
Decreases Sympathetic Activity

Cardiac preload is the initial stretching
of cardiac muscle to accommodate the
blood that fills the heart prior to heart
contraction. This directly impacts how
much blood fills in the heart. Afterload
is the force required by the heart to eject
blood to the rest of the body.

The physiological benefits the SGLT2i
provides - such as glucosuria, osmotic
diuresis, reduction of blood pressure,
and no observed increase in heart rate -
suggests the dampening of the sympathetic
nervous system.

The SGLT2i causes decreased preload
and afterload, resulting in enhanced blood
flow out of the heart and reduction of
blood pressure.

The sympathetic nervous system is
responsible for directing fight or flight
responses in dangerous or stressful
situations. This involves an increase in heart
rate and blood pressure, pupil dilation, and
increased body temperature.

Circulation: the SGLT2i reduces
Systolic Blood Pressure and
Increases Hematocrit

By avoiding these responses, the
SGLT2i ameliorates cardiac, renal,
immunological, and nervous system stress.

	 By virtue of the SGLT2i's ability
to reduce preload and afterload, it in
turn reduces systolic blood pressure.
The SGLT2i also augments the rate of
erythropoiesis: the production of red
blood cells. This subsequently raises the
hematocrit level, which is the ratio of red
blood cells to total blood volume.

Conclusions
The Benefits of SGLT2i Outweigh
the Unfavorable Side Effects

Lowered systolic blood pressure paired
with an increased hematocrit content
results in bettered blood circulation.
Figure 14: Dapagliflozin reduces renal risk
by 39% and overall mortality risk by 31%
(DAPA-CKD)

Kidney: The SGLT2i Decreases
Sodium/Glucose Reabsorption
and Increases Osmotic Diuresis

We can now conclude that the SGLT2i
is renal protective in patients with Chronic
Kidney Disease. This is yet another
example of how the SGLT2i is capable
of treatment beyond just the scope of
diabetes.

	 As detailed when previously
discussing the mechanism of the SGLT2i,
reabsorption of glucose is reduced thereby
increasing urinary glucose excretion. This
coupled with the reduction of sodium
reabsorption allows for an increase of
sodium delivery to the kidney's distal
tubule.

How does the SGLT2i
accomplish this?

This influences several functions
including lowering of cardiac preload and
afterload while also decreasing sympathetic
activity of the nervous system.
The combination of these physiological
responses improves overall kidney function
and outcomes.

Figure 15: the SGLT2i offers novel
pathways in preventing and treating heart
failure
12 CHESTER COUNT Y Medicine | SPRING 2021

Figure 16: the pros of the SGLT2i outweigh
the cons

Pros
* Prevention of incident and treatment
of established heart failure
* Preservation of renal function
* Reduction of major adverse
cardiovascular events
* Reduction of blood pressure
* Weight loss
* Improvement in glycemia

Cons
* Genital Infections
* Diabetic Ketoacidosis
* Hypovolemia
http://www.chestercms.org
Chester County Medicine Spring 2021

Table of Contents for the Digital Edition of Chester County Medicine Spring 2021
