Chester County Medicine Spring 2021 - 10

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The SGLT2i: Teaching Us to Know Diabetes by Heart
continued from page 9

body's cells. Elevated blood sugar levels can
result in circulatory, nervous, and immune
system disorders.
As it is heavily intertwined with the
cardiovascular system, Type 2 Diabetes
Mellitus can create a harmful loop between
instances of heart failure and diabetic
kidney disease.

antidiabetic drugs that inhibit the kidneys
from reabsorbing glucose by excreting
glucose via urine. Unlike other common
antidiabetic medications, the SGLT2i
functions independently of insulin, thus
granting better control over glucose levels.

Symptomatology
* Increased thirst and hunger
* Frequent urination
* Unintended weight loss

Mechanism of SGLT2 and
inhibitor
The kidneys are responsible for
managing the body's waste products and
excess fluid through urine. Non-diabetics
approximately filter 180 grams of glucose
per day through the kidney.

Figure 5: A doctor prescribes an SGLT2i
treatment for a patient
Figure 4: The vicious circles between Type
2 Diabetes, Kidney Disease, and Heart
Failure

to help treat diabetes: canagliflozin,
dapagliflozin, and empagliflozin.

History of the SGLT2i
The adage " an apple a day keeps the
doctor away " is rooted in some truth. In
1835, French chemists isolated a substance
called phlorizin from the bark of an apple
tree. Due to its fever reducing abilities
and capacity to fight infectious disease,
phlorizin was primarily utilized to treat
malaria until the late 1800s.

As aforementioned, this filtered
glucose is then reabsorbed into the body
alongside sodium ions via the Sodium
Glucose cotransporter 2, a protein found
in the proximal tubule of kidney cells. The
inhibitor interrupts this function of the
cotransporter, ultimately decreasing the
amount of sugar and sodium present in the
blood.

Causes
Type 2 Diabetes results from 2
interrelated issues:

Figure 7: Mechanism of the SGLT2 and its
inhibitor

1. Muscle, fat, and liver cells stop
responding to insulin
2. The pancreas ceases to produce
insulin

Treatments and Medications
Healthy eating, regular exercise, and
weight loss can all help manage Type 2
Diabetes. Additionally, diet and exercise
can be supplemented with drug treatments
including metformin, sulfonylureas, and
sodium glucose co-transporter 2 inhibitors
(SGLT2i).
What is the SGLT2i?
The Sodium Glucose coTransporter
2 inhibitors (SGLT2i) are a class of

Figure 6: An apple tree
In 1886 phlorizin was found to have
glucosuric properties, meaning it elevates
the amount of sugar present in urine.
Upon further investigation in the 1900s,
phlorizin was identified to act on the
proximal tubules of the kidneys. This is
where glucose is reabsorbed from urine
filtrate back into the bloodstream. With
this knowledge, phlorizin was realized as a
novel treatment for hyperglycemia in the
1980s.
In the 2010s, the following 3 derivatives
of phlorizin were approved by the FDA

10 CHESTER COUNT Y Medicine | SPRING 2021

Due to the SGLT2i's impact on sodium
retention and the cardiovascular system,
the FDA sought to establish studies to
determine whether this therapy would
cause unacceptable cardiovascular risks.

Figure 8: The SGLT2i lead us down an
unprecedented but welcomed road in
medicine
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