PKD Life - Fall 2022 - 22

ANIMATED HEALTHCARE LTD./SCIENCE SOURCE
THE RESEARCH REPORT
Can Diabetes Drugs
Treat ADPKD?
Preliminary research suggests that these
medications may help slow kidney damage.
By Debra Gordon
C an drugs that are used to treat type 2 diabetes
help slow kidney damage in people with autosomal
dominant polycystic kidney disease (ADPKD)?
That's a question currently being investigated by
PKD researchers.
A small study looking at the drug metformin, which
has been used to treat diabetes for more than half a
century, suggests that it may improve markers associated
with the progression of ADPKD. In addition, other
researchers will soon launch a new study looking
at the effectiveness of another diabetes medication,
empagliflozin.
HOW METFORMIN WORKS
Although it's primarily prescribed for diabetes, metformin
has been studied as a possible treatment for
numerous metabolic conditions, as well as an antiaging
drug and for cancer.
In people with diabetes, it works by reducing the
amount of glucose, or sugar, the body produces and
absorbs and by increasing the body's response to
insulin. Terry J. Watnick, M.D., the Joan B. and John H.
Sadler, M.D., professor in nephrology at the University
of Maryland School of Medicine in Baltimore, has
studied metformin and says the drug's role in ADPKD
may be related to the effect that it has on mitochondria,
known as the cell's powerhouse, which makes
adenosine triphosphate (ATP), the cell's main energycarrying
molecule.
22 PKD LIFE * FALL 2022
" Recent data showed
that PKD is associated with
increased use of ATP and
energy, also known as the
Warburg effect, " Dr. Watnick
says. " That's a feature we see
in a lot of cancers. And when
you use a lot of energy, you're
in a pro-growth situation,
meaning cells multiply and
grow. In cancer, that's a bad
thing because it means the
cancer cells can overwhelm
normal cells; in ADPKD, it's a
bad thing because it contributes
to the growth of the cysts
that eventually damage the
kidney beyond repair. "
Metformin targets an
enzyme that plays a vital role
in cell metabolism, reducing
energy production and cellular
growth. It also has actions
against other molecular mechanisms
believed to be involved
with ADPKD, including reducing
the activity of the CFTR
channel protein, which also is
thought to increase cyst fluid.
Some studies in animal
models of ADPKD find that
metformin reduces cyst formation
and growth. To learn
if it was safe and effective in
humans, Dr. Watnick and her
co-investigators randomized
97 people with ADPKD and
a glomerular filtration rate
(or GFR, a measure of how
well the kidneys are filtering
blood) of more than 50 mL/
min/1.73 m2
, to either metformin
or placebo (a sugar pill)
twice daily.
After two years, 38 participants
in the metformin arm
and 39 in the placebo arm
were still active in the study;
the rest had dropped out
primarily because of gastrointestinal
issues, such as
nausea. There were no other
safety issues. The researchers
found a slight slowing in the
rate of decline of GFR in the
metformin arm. However,
this effect was not statistically
significant. While the results
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