The Journal of Clinical Pharmacology,
Journal Year:
2024,
Volume and Issue:
64(10), P. 1204 - 1221
Published: June 26, 2024
Obesity
is
a
disease
of
epidemic
proportions
in
the
United
States
and
contributes
to
morbidity
mortality
for
large
part
population.
In
addition,
financial
costs
this
society
are
high.
Lifestyle
modifications
key
prevention
treatment
but
adherence
long-term
success
have
been
challenging.
Bariatric
surgery
has
available
pharmacologic
approaches,
first
developed
1950s,
continue
be
an
option;
however,
existing
formulations
not
provided
optimal
clinical
efficacy
had
many
concerning
adverse
effects.
Over
last
decade,
glucagon-like
peptide-1
(GLP-1)
receptor
agonists,
novel
group
medications
type
2
diabetes,
were
found
produce
significant
weight
loss.
Several
formulations,
at
higher
doses,
received
FDA
approval
obesity
or
those
overweight
with
weight-related
co-morbidities.
More
hormone-based
therapies
being
developed,
some
dual
triple-receptor
agonist
activity.
Their
use,
without
questions
concerns
as
safety
efficacy,
problems
cost
reimbursement,
how
their
use
may
intersect
public
health
efforts
manage
epidemic.
This
review
will
focus
on
GLP-1
agonists
currently
used
loss
discuss
pharmacology,
pertinent
research
findings
establishing
benefits
risks,
issues
prescribing
these
medications,
perspective
from
point
view.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Sept. 18, 2024
The
glucagon-like
peptide-1
(GLP-1)
receptor,
known
as
GLP-1R,
is
a
vital
component
of
the
G
protein-coupled
receptor
(GPCR)
family
and
found
primarily
on
surfaces
various
cell
types
within
human
body.
This
specifically
interacts
with
GLP-1,
key
hormone
that
plays
an
integral
role
in
regulating
blood
glucose
levels,
lipid
metabolism,
several
other
crucial
biological
functions.
In
recent
years,
GLP-1
medications
have
become
focal
point
medical
community
due
to
their
innovative
treatment
mechanisms,
significant
therapeutic
efficacy,
broad
development
prospects.
article
thoroughly
traces
developmental
milestones
drugs,
from
initial
discovery
clinical
application,
detailing
evolution
diverse
along
distinct
pharmacological
properties.
Additionally,
this
paper
explores
potential
applications
agonists
(GLP-1RAs)
fields
such
neuroprotection,
anti-infection
measures,
reduction
inflammation,
enhancement
cardiovascular
function.
It
provides
in-depth
assessment
effectiveness
GLP-1RAs
across
multiple
body
systems-including
nervous,
cardiovascular,
musculoskeletal,
digestive
systems.
includes
integrating
latest
trial
data
delving
into
signaling
pathways
mechanisms.
primary
goal
emphasize
extensive
benefits
using
treating
spectrum
diseases,
obesity,
non-alcoholic
fatty
liver
disease
(NAFLD),
neurodegenerative
musculoskeletal
forms
cancer.
ongoing
new
indications
for
drugs
offers
promising
prospects
further
expanding
interventions,
showcasing
field.
Obesity Facts,
Journal Year:
2024,
Volume and Issue:
17(4), P. 374 - 444
Published: Jan. 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.
Clinical and Molecular Hepatology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 19, 2024
As
the
rates
of
obesity
and
type
2
diabetes
(T2D)
continue
to
increase
globally,
so
does
prevalence
metabolic
dysfunction
associated
steatotic
liver
disease
(MASLD).
Currently,
38%
all
adults
7-14%
children
adolescents
have
MASLD.
By
2040,
MASLD
rate
for
is
projected
over
55%.
Although
many
with
will
not
develop
progressive
disease,
given
vast
number
patients
MASLD,
it
has
now
become
top
indication
transplant
in
United
States
those
hepatocellular
carcinoma
(HCC)
women.
However,
most
common
cause
mortality
among
remains
death
cardiovascular
diseases.
In
addition
outcomes
(cirrhosis
HCC),
increased
risk
developing
de-novo
T2D,
chronic
kidney
sarcopenia
extrahepatic
cancers.
Furthermore,
decreased
health
related
quality
life,
work
productivity,
fatigue
healthcare
resource
utilization
substantial
economic
burden.
Similar
other
lifestyle
interventions
heathy
diet
physical
activity
remain
cornerstone
managing
these
patients.
a
T2D
drugs
are
available
treat
co-morbid
Resmetirom
only
MASH-targeted
medication
that
was
recently
approved
by
Federal
Drug
Administration
use
stage
2-3
fibrosis.
The
following
review
provides
an
overview
epidemiology,
its
factors
demonstrates
without
further
global
initiatives,
may
increase.
Alimentary Pharmacology & Therapeutics,
Journal Year:
2024,
Volume and Issue:
60(11-12), P. 1525 - 1533
Published: Oct. 16, 2024
ABSTRACT
Background
Semaglutide,
a
glucagon‐like
peptide‐1
receptor
agonist,
has
demonstrated
potential
beneficial
effects
in
metabolic
dysfunction‐associated
steatohepatitis
(MASH).
Aims
To
describe
the
trial
design
and
baseline
characteristics
of
‘Effect
Semaglutide
Subjects
with
Non‐cirrhotic
Non‐alcoholic
Steatohepatitis’
(ESSENCE)
(NCT04822181).
Methods
ESSENCE
is
two‐part,
phase
3,
randomised,
multicentre
evaluating
effect
subcutaneous
semaglutide
2.4
mg
participants
biopsy‐proven
MASH
fibrosis
stage
2
or
3.
The
primary
objective
Part
1
to
demonstrate
that
improves
liver
histology
compared
placebo.
two
endpoints
are:
resolution
no
worsening
fibrosis,
improvement
steatohepatitis.
based
on
clinical
outcomes.
current
work
reports
first
800
randomised
which
includes
demographics,
laboratory
parameters,
histology,
non‐invasive
tests
presence
steatotic
disease
(MASLD)
cardiometabolic
criteria.
Results
Of
participants,
250
(31.3%)
had
550
(68.8%)
In
overall
population,
mean
(standard
deviation
[SD])
age
was
56
(11.6)
years,
57.1%
were
female,
(SD)
body
mass
index
34.6
(7.2)
kg/m
,
55.5%
type
diabetes
>
99%
at
least
one
MASLD
criterion
according
published
definition.
Conclusion
population
clinically
significant
stages
Although
criteria
not
requirement
for
study
enrolment,
almost
all
(>
99%)
criterion.
Trial
Registration
NCT04822181
Hepatology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 19, 2024
Metabolic
dysfunction–associated
steatotic
liver
disease,
formerly
known
as
NAFLD,
has
ascended
to
prominence
the
predominant
chronic
disease
in
Western
countries
and
now
stands
a
leading
cause
of
transplantations.
In
more
advanced
stage,
metabolic
steatohepatitis
(MASH)
may
lead
fibrosis,
gateway
cirrhosis,
cancer,
failure.
Despite
extensive
research
exploration
various
drug
mechanisms,
anticipation
for
inaugural
approved
materialize
by
2024
is
palpable,
marking
significant
milestone.
Numerous
pathways
have
been
investigated
MASH
treatment,
exploring
thyroid
hormone
receptors,
glucagon-like
peptides
1,
peroxisome
proliferator–activated
agents
influencing
hepatic
steatosis
synthesis,
inflammatory
pathways,
genetic
components,
fibrosis
an
array
other
avenues.
Over
time,
key
regulatory
directions
crystallized,
manifesting
2
primary
endpoints
under
investigation:
resolution
without
worsening
and/or
improvement
stage
steatohepatitis,
especially
used
phase
3
clinical
trials,
while
alternative
noninvasive
are
explored
trials.
The
prospect
proving
efficacy
trials
opens
doors
combination
therapies,
evaluating
ideal
drugs
yield
comprehensive
benefits,
extending
beyond
organs.
Certain
already
underway.
this
review,
we
discuss
forefront
2023/2024,
illuminating
outcomes,
future
trajectories.
Furthermore,
tackle
challenges
confronting
propose
potential
strategies
surmounting
them.
