Key
Takeaways
-
In
adults,
GLP-1
receptor
agonists
have
been
linked
to
elevated
risks
of
gallbladder
and
biliary
disease. -
In
a
new
study,
retrospective
data
linked
GLP-1
drug
use
in
youth
to
higher
risks
of
biliary
colic
and
cholecystectomy. -
The
researchers
urged
vigilance
for
biliary
symptoms
stemming
from
rapid
weight
loss
and
gallbladder
dysmotility
with
GLP-1
drugs.
Use
of
GLP-1
receptor
agonists
was
associated
with
increased
cumulative
gallbladder
and
biliary
events
in
youths,
according
to
a
retrospective
analysis
of
TriNetX
data.
Among
over
37,000
adolescents
and
young
adults
with
overweight
or
obesity,
GLP-1
drug
use
was
associated
with
increased
risks
of
biliary
colic
(RR
1.62,
95%
CI
1.28-2.04,
P<0.001)
and
cholecystectomy
(RR
1.39,
95%
CI
1.04-1.87,
P=0.03)
compared
with
matched
controls,
but
not
with
cholecystitis,
reported
Josélio
Rodrigues
de
Oliveira
Filho,
MD,
of
Mass
General
Brigham
and
Harvard
Medical
School
in
Boston,
and
colleagues.
Lag
analyses
and
12-month
administrative
censoring
yielded
similar
results,
the
researchers
wrote
in
a
JAMA
Pediatrics
research
letter.
Time-to-event
analyses
showed
higher
effect
estimates
across
all
three
biliary
outcomes:
-
Cholecystitis:
HR
2.22,
95%
CI
1.51-3.25,
P<0.001 -
Biliary
colic:
HR
2.92,
95%
CI
2.29-3.71,
P<0.001 -
Cholecystectomy:
HR
2.39,
95%
CI
1.77-3.22,
P<0.001
“The
observed
biliary
risk
likely
reflects
rapid
weight
loss,
which
predisposes
to
gallstone
formation
in
children
with
obesity,
compounded
by
GLP-1
receptor
agonist-mediated
gallbladder
dysmotility,”
the
authors
explained.
“These
findings
suggest
vigilance
for
biliary
symptoms
is
needed
when
prescribing
GLP-1
receptor
agonists
to
youths,”
they
advised.
This
safety
signal
was
first
flagged
in
adolescents
during
the
STEP
TEENS
trial,
where
4%
of
participants
in
the
semaglutide
(Wegovy)
arm
developed
acute
gallbladder
disease
compared
with
none
in
the
placebo
arm.
In
contrast,
the
SCALE
Teens
and
SCALE
Kids
trials
of
liraglutide
(Saxenda)
did
not
mention
biliary
events.
Biliary
events
have
also
been
reported
in
adults
using
GLP-1
drugs,
the
authors
added.
A
2022
meta-analysis
of
76
randomized
clinical
trials
in
adults
linked
GLP-1
drug
use
to
elevated
risks
of
gallbladder
and
biliary
disease,
particularly
when
used
at
higher
doses
for
weight
loss.
While
this
elevated
risk
was
significant,
the
meta-analysis
authors
noted
that
the
overall
absolute
risk
increase
was
small,
at
only
an
additional
27
cases
per
10,000
persons
treated
per
year.
“Adult
data
suggest
a
pharmacologic
mechanism,”
Rodrigues
de
Oliveira
Filho’s
group
noted.
For
the
current
study,
researchers
evaluated
patients
ages
12
to
21
years
diagnosed
with
overweight
or
obesity
between
January
2022
and
May
2026
using
ICD-10
codes.
Propensity
score
matching
yielded
18,759
individuals
each
in
the
GLP-1
drug
and
control
groups.
In
the
GLP-1
drug
group,
the
mean
age
was
17.4
years,
63.0%
were
female,
and
median
follow-up
was
364
days.
The
most
commonly
used
GLP-1
agent
was
semaglutide
(76.7%),
followed
by
liraglutide
(14.5%),
dulaglutide
(Trulicity;
8.6%),
tirzepatide
(Zepbound;
3.4%),
and
exenatide
(Byetta,
Bydureon;
0.6%).
In
subgroup
analyses,
youths
with
class
I
or
class
II
obesity
(body
mass
index
[BMI]
30-39.9)
had
elevated
hazard
rates
over
time
for
cholecystitis
(HR
3.36),
biliary
colic
(HR
2.78),
and
cholecystectomy
(HR
2.93).
Event
counts
were
insufficient
for
meaningful
analysis
in
the
overweight
(BMI
25-29.9)
and
class
III
obesity
(BMI
40
or
higher)
subgroups.
The
authors
emphasized
that
the
study’s
retrospective
design
and
reliance
on
diagnostic
codes
prevent
establishing
causality.
Additionally,
the
data
lacked
details
on
GLP-1
drug
dose,
treatment
duration,
total
weight
loss,
and
gallbladder
imaging.
“Prospective
studies
should
clarify
risk
stratification,
evaluate
whether
prophylactic
strategies
used
in
bariatric
populations
could
be
applied,
and
identify
whether
monitoring
protocols
can
reduce
biliary
morbidity,”
the
authors
recommended.
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