Expert Opinion on Investigational Drugs,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 27, 2025
Glucagon-like
peptide-1
receptor
agonists
(GLP-1RAs),
and
dual
GLP-1/glucose-dependent
insulinotropic
peptide
(GIP)
or
glucagon
have
emerged
as
promising
agents
to
treat
metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)/metabolic
steatohepatitis
(MASH).
Although
the
beneficial
effects
of
GLP-1RAs
on
glycemic
control
weight
are
well-established,
clinicians
may
be
unfamiliar
with
other
potential
benefits
this
class.
We
examined
pleiotropic
how
they
relate
gastroenterologists
for
MASLD/MASH
treatment.
Our
narrative
review
English
articles
included
four
(subcutaneous
semaglutide,
liraglutide,
dulaglutide,
efpeglenatide),
a
GLP-1/GIP
agonist
(tirzepatide),
GLP-1/glucagon
(survodutide),
MASLD/MASH,
related
disorders,
clinical
management,
treatment
outcomes
landscape.
In
Phase
I
-
III
trials,
associated
clinically
relevant
hepatic
improvements
including
MASH
resolution,
fat
reduction,
preventing
worsening
fibrosis.
Effects
cardiometabolic
parameters
align
type
2
diabetes/obesity
data,
comprising
substantial
in
glycemic,
weight,
cardiovascular
outcomes.
Promising
data
also
suggest
common
comorbidities,
obstructive
sleep
apnea,
polycystic
ovary
syndrome,
chronic
kidney
disease,
heart
failure
preserved
ejection
fraction.GLP-1RAs
represent
valuable
pharmacotherapeutic
option
managing
individuals
comorbid
conditions.
JAMA,
Год журнала:
2023,
Номер
330(20), С. 2000 - 2000
Опубликована: Ноя. 28, 2023
Importance
Obesity
affects
approximately
42%
of
US
adults
and
is
associated
with
increased
rates
type
2
diabetes,
hypertension,
cardiovascular
disease,
sleep
disorders,
osteoarthritis,
premature
death.
Observations
A
body
mass
index
(BMI)
25
or
greater
commonly
used
to
define
overweight,
a
BMI
30
obesity,
lower
thresholds
for
Asian
populations
(BMI
≥25-27.5),
although
use
alone
not
recommended
determine
individual
risk.
Individuals
obesity
have
higher
incident
disease.
In
men
39,
event
are
20.21
per
1000
person-years
compared
13.72
in
normal
BMI.
women
39.9,
9.97
6.37
Among
people
5%
10%
weight
loss
improves
systolic
blood
pressure
by
about
3
mm
Hg
those
may
decrease
hemoglobin
1c
0.6%
1%
diabetes.
Evidence-based
treatment
includes
interventions
addressing
5
major
categories:
behavioral
interventions,
nutrition,
physical
activity,
pharmacotherapy,
metabolic/bariatric
procedures.
Comprehensive
care
plans
combine
appropriate
patients.
Multicomponent
ideally
consisting
at
least
14
sessions
6
months
promote
lifestyle
changes,
including
components
such
as
self-monitoring,
dietary
activity
counseling,
problem
solving,
often
produce
loss,
regain
occurs
25%
more
participants
2-year
follow-up.
Effective
nutritional
approaches
focus
on
reducing
total
caloric
intake
strategies
based
patient
preferences.
Physical
without
calorie
reduction
typically
causes
less
(2-3
kg)
but
important
weight-loss
maintenance.
Commonly
prescribed
medications
antidepressants
(eg,
mirtazapine,
amitriptyline)
antihyperglycemics
glyburide
insulin
cause
gain,
clinicians
should
review
consider
alternatives.
Antiobesity
nonpregnant
patients
overweight
weight-related
comorbidities
conjunction
modifications.
Six
currently
approved
the
Food
Drug
Administration
long-term
use:
glucagon-like
peptide
receptor
1
(GLP-1)
agonists
(semaglutide
liraglutide
only),
tirzepatide
(a
glucose-dependent
insulinotropic
polypeptide/GLP-1
agonist),
phentermine-topiramate,
naltrexone-bupropion,
orlistat.
Of
these,
has
greatest
effect,
mean
21%
72
weeks.
Endoscopic
procedures
(ie,
intragastric
balloon
endoscopic
sleeve
gastroplasty)
can
attain
13%
months.
Weight
from
metabolic
bariatric
surgeries
laparoscopic
gastrectomy
Roux-en-Y
gastric
bypass)
ranges
30%
12
Maintaining
difficult,
clinical
guidelines
support
antiobesity
when
maintenance
inadequate
alone.
Conclusion
Relevance
US.
Behavioral
GLP-1
8%
surgery
loss.
Comprehensive,
evidence-based
combines
Obesity Facts,
Год журнала:
2024,
Номер
17(4), С. 374 - 444
Опубликована: Янв. 1, 2024
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD),
previously
termed
non-alcoholic
fatty
(NAFLD),
is
defined
as
(SLD)
in
the
presence
of
one
or
more
cardiometabolic
risk
factor(s)
and
absence
harmful
alcohol
intake.
The
spectrum
MASLD
includes
steatosis,
metabolic
steatohepatitis
(MASH,
NASH),
fibrosis,
cirrhosis
MASH-related
hepatocellular
carcinoma
(HCC).
This
joint
EASL-EASD-EASO
guideline
provides
an
update
on
definitions,
prevention,
screening,
diagnosis
treatment
for
MASLD.
Case-finding
strategies
with
using
non-invasive
tests,
should
be
applied
individuals
factors,
abnormal
enzymes,
and/or
radiological
signs
hepatic
particularly
type
2
diabetes
(T2D)
obesity
additional
factor(s).
A
stepwise
approach
blood-based
scores
(such
FIB-4)
and,
sequentially,
imaging
techniques
transient
elastography)
suitable
to
rule-out/in
advanced
which
predictive
liver-related
outcomes.
In
adults
MASLD,
lifestyle
modification
-
including
weight
loss,
dietary
changes,
physical
exercise
discouraging
consumption
well
optimal
management
comorbidities
use
incretin-based
therapies
(e.g.
semaglutide,
tirzepatide)
T2D
obesity,
if
indicated
advised.
Bariatric
surgery
also
option
obesity.
If
locally
approved
dependent
label,
non-cirrhotic
MASH
significant
fibrosis
(stage
≥2)
considered
a
MASH-targeted
resmetirom,
demonstrated
histological
effectiveness
acceptable
safety
tolerability
profile.
No
pharmacotherapy
can
currently
recommended
cirrhotic
stage.
Management
adaptations
drugs,
nutritional
counselling,
surveillance
portal
hypertension
HCC,
transplantation
decompensated
cirrhosis.
JAMA,
Год журнала:
2024,
Номер
332(7), С. 571 - 571
Опубликована: Авг. 20, 2024
Obesity
affects
approximately
19%
of
women
and
14%
men
worldwide
is
associated
with
increased
morbidity.
Antiobesity
medications
(AOMs)
modify
biological
processes
that
affect
appetite
significantly
improve
outcomes,
such
as
type
2
diabetes,
hypertension,
dyslipidemia.
Pharmacology & Therapeutics,
Год журнала:
2023,
Номер
251, С. 108549 - 108549
Опубликована: Окт. 23, 2023
Obesity
and
its
comorbidities,
including
type
2
diabetes
mellitus,
cardiovascular
disease,
heart
failure
non-alcoholic
liver
disease
are
a
major
health
economic
burden
with
steadily
increasing
numbers
worldwide.
The
need
for
effective
pharmacological
treatment
options
is
strong,
but,
until
recently,
only
few
drugs
have
proven
sufficient
efficacy
safety.
This
article
provides
comprehensive
overview
of
obesity
special
focus
on
organ-specific
pathomechanisms.
Bariatric
surgery
as
the
so
far
most-effective
therapeutic
strategy,
current
future
strategies
will
be
discussed.
An
knowledge
about
gut-brain
axis
especially
identification
physiology
incretins
unfolds
high
number
potential
drug
candidates
impressive
weight-reducing
potential.
Future
multi-modal
concepts
in
may
surpass
effectivity
bariatric
not
regard
to
weight
loss,
but
also
associated
comorbidities.
Frontiers in Pharmacology,
Год журнала:
2023,
Номер
14
Опубликована: Июнь 20, 2023
Obesity
affects
more
than
10%
of
the
adult
population
globally.
Despite
introduction
diverse
medications
aimed
at
combating
fat
accumulation
and
obesity,
a
significant
number
these
pharmaceutical
interventions
are
linked
to
substantial
occurrences
severe
adverse
events,
occasionally
leading
their
withdrawal
from
market.
Natural
products
serve
as
attractive
sources
for
anti-obesity
agents
many
them
can
alter
host
metabolic
processes
maintain
glucose
homeostasis
via
thermogenic
stimulation,
appetite
regulation,
pancreatic
lipase
amylase
inhibition,
insulin
sensitivity
enhancing,
adipogenesis
inhibition
adipocyte
apoptosis
induction.
In
this
review,
we
shed
light
on
biological
that
control
energy
balance
thermogenesis
well
pathways
in
white
adipose
tissue
browning,
also
highlight
potential
natural
with
mechanism
action.
Based
previous
findings,
crucial
proteins
molecular
involved
browning
lipolysis
induction
uncoupling
protein-1,
PR
domain
containing
16,
peroxisome
proliferator-activated
receptor-γ
addition
Sirtuin-1
AMP-activated
protein
kinase
pathway.
Given
some
phytochemicals
lower
proinflammatory
substances
like
TNF-α,
IL-6,
IL-1
secreted
change
production
adipokines
leptin
adiponectin,
which
important
regulators
body
weight,
represent
treasure
trove
agents.
conclusion,
conducting
comprehensive
research
holds
accelerate
development
an
improved
obesity
management
strategy
characterized
by
heightened
efficacy
reduced
incidence
side
effects.
BMJ,
Год журнала:
2024,
Номер
unknown, С. e072686 - e072686
Опубликована: Март 25, 2024
Abstract
Recent
publicity
around
the
use
of
new
antiobesity
medications
(AOMs)
has
focused
attention
patients
and
healthcare
providers
on
role
pharmacotherapy
in
treatment
obesity.
Newer
drug
treatments
have
shown
greater
efficacy
safety
compared
with
older
treatments,
yet
access
to
these
is
limited
by
providers’
discomfort
prescribing,
bias,
stigma
obesity,
as
well
lack
insurance
coverage.
Now
more
than
ever,
must
be
able
discuss
risks
benefits
full
range
available
patients,
incorporate
both
guideline
based
advice
emerging
real
world
clinical
evidence
into
daily
practice.
The
tremendous
variability
response
means
that
clinicians
need
a
flexible
approach
takes
advantage
specific
features
medication
selected
provide
best
option
for
individual
patients.
Future
research
needed
how
practice
settings,
potential
combination
therapies,
cost
effectiveness
medications.
Several
are
being
evaluated
ongoing
trials,
suggesting
future
obesity
bright.
