BMJ Open Diabetes Research & Care,
Journal Year:
2024,
Volume and Issue:
12(4), P. e004291 - e004291
Published: Aug. 1, 2024
The
prevalence
of
type
2
diabetes
(T2D)
is
increasing
relentlessly
all
over
the
world,
in
parallel
with
a
similar
increase
obesity,
and
striking
ever
younger
patients.
Only
minority
patients
T2D
attain
glycemic
targets,
indicating
clear
need
for
novel
antidiabetic
drugs
that
not
only
control
glycemia
but
also
halt
or
slow
progressive
loss
β-cells.
Two
entirely
classes
agents—glucokinase
activators
imeglimin—have
recently
been
approved
will
be
subject
this
review.
Allosteric
glucokinase,
an
enzyme
stimulating
insulin
secretion
β-cells
suppressing
hepatic
glucose
production,
are
oral
low-molecular-weight
drugs.
One
these,
dorzagliatin,
China
use
adult
T2D,
either
as
monotherapy
add-on
to
metformin.
It
remains
seen
whether
drug
produce
sustained
effects
many
years
side
led
discontinuation
early
candidates
limit
usefulness
dorzagliatin.
Imeglimin—which
shares
structural
similarities
metformin—targets
mitochondrial
dysfunction
was
Japan
against
T2D.
In
preclinical
studies,
has
shown
promising
β-cell
protective
preservative
may
translate
into
disease-modifying
effects.
Hopefully,
these
two
newcomers
contribute
filling
great
medical
new
treatment
modalities,
preferably
potential.
where
they
fit
contemporary
algorithms,
which
combinations
effective
should
avoided.
Time
tell
what
extent
agents
add
value
current
options
terms
effect,
acceptable
safety,
utility
combination
therapy,
impact
on
hard
end-points
such
cardiovascular
disease.
Endocrinology and Metabolism,
Journal Year:
2024,
Volume and Issue:
39(1), P. 12 - 22
Published: Feb. 15, 2024
Obesity
is
the
fifth
leading
risk
factor
for
global
deaths
with
numbers
continuing
to
increase
worldwide.
In
last
20
years,
emergence
of
pharmacological
treatments
obesity
based
on
gastrointestinal
hormones
has
transformed
therapeutic
landscape.
The
successful
development
glucagon-like
peptide-1
(GLP-1)
receptor
agonists,
followed
by
synergistic
combined
effect
glucose-dependent
insulinotropic
polypeptide
(GIP)/GLP-1
agonists
achieved
remarkable
weight
loss
and
glycemic
control
in
those
diseases
type
2
diabetes.
multiple
cardiometabolic
benefits
include
improving
control,
lipid
profiles,
blood
pressure,
inflammation,
hepatic
steatosis.
2023
phase
double-blind,
randomized
controlled
trial
evaluating
a
GLP-1/GIP/glucagon
triagonist
(retatrutide)
patients
disease
reported
24.2%
at
48
weeks
12
mg
retatrutide.
This
review
evaluates
current
available
evidence
GLP-1
dual
GLP-1/GIP
co-agonists
focus
triagonists
discusses
potential
future
research
directions.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(6), P. 1320 - 1320
Published: June 13, 2024
Guidelines
for
the
management
of
obesity
and
type
2
diabetes
(T2DM)
emphasize
importance
lifestyle
changes,
including
a
reduced-calorie
diet
increased
physical
activity.
However,
many
people,
these
changes
can
be
difficult
to
maintain
over
long
term.
Medication
options
are
already
available
treat
obesity,
which
help
reduce
appetite
and/or
caloric
intake.
Incretin-based
peptides
exert
their
effect
through
G-protein-coupled
receptors,
receptors
glucagon-like
peptide-1
(GLP-1)
glucose-dependent
insulinotropic
polypeptide
(GIP),
glucagon
peptide
hormones
important
regulators
insulin
secretion
energy
metabolism.
Understanding
role
intercellular
signaling
pathways
inflammatory
processes
is
essential
development
effective
pharmacological
agents
in
obesity.
GLP-1
receptor
agonists
have
been
successfully
used,
but
it
assumed
that
effectiveness
may
limited
by
desensitization
downregulation
target
receptor.
A
growing
number
new
acting
on
incretin
becoming
everyday
clinical
practice,
oral
agonists,
dual
GLP-1/GIP
agonist
tirzepatide,
other
triple
GLP-1/GIP/glucagon
show
further
significant
therapeutic
potential.
This
narrative
review
summarizes
effects
different
presents
future
prospects
treatment
T2DM
Peptides,
Journal Year:
2024,
Volume and Issue:
173, P. 171149 - 171149
Published: Jan. 5, 2024
Options
for
the
treatment
of
type
2
diabetes
mellitus
(T2DM)
and
obesity
have
recently
been
expanded
by
results
several
large
clinical
trials
with
incretin-based
peptide
therapies.
Most
these
studies
conducted
glucagon-like
peptide-1
(GLP-1)
receptor
agonist
semaglutide,
which
is
available
as
a
once
weekly
subcutaneous
injection
daily
tablet,
injected
dual
tirzepatide,
interacts
receptors
GLP-1
glucose-dependent
insulinotropic
polypeptide
(GIP).
In
individuals
T2DM
therapies
achieved
reductions
glycated
haemoglobin
(HbA1c)
>
2%
lowered
body
weight
10%.
some
studies,
agents
tested
in
non-diabetic,
obese
at
much
higher
doses
15%.
Emerging
evidence
suggests
can
also
offer
cardio-protective
potentially
reno-protective
effects.
Other
early
development,
notably
triple
GLP-1/GIP/glucagon
(retatrutide)
combination
semaglutide
amylin
analogue
cagrilintide
(CagriSema),
shown
strong
efficacy.
Although
incretin
incur
adverse
gastrointestinal
effects
are
most
patients
mild-to-moderate
transient
but
result
cessation
cases.
Thus,
efficacy
new
enhancing
opportunity
to
control
blood
glucose
improve
obesity.
Peptides,
Journal Year:
2025,
Volume and Issue:
187, P. 171380 - 171380
Published: March 11, 2025
Recent
studies
with
peptide-based
incretin
herapies
have
focussed
mainly
on
the
glucagon-like
peptide-1
(GLP-1)
receptor
agonist
semaglutide
and
dual
tirzepatide
that
engages
receptors
for
GLP-1
glucose-dependent
insulinotropic
polypeptide
(GIP).
Randomised
clinical
trials
'real-world'
confirmed
marked
glucose-lowering
weight-lowering
efficacy
of
these
agents
across
diverse
populations.
These
include
different
ethnic
groups,
young
elderly
individuals
without
diabetes
and/or
overweight
or
obesity.
also
protections
against
development
progression
cardiovascular
renal
diseases
are
additive
to
benefits
conferred
by
improved
control
blood
glucose
body
weight.
Emerging
evidence
suggests
therapies
could
additionally
ameliorate
fatty
liver
disease,
chronic
inflammation,
sleep
apnea
possibly
degenerative
bone
disorders
cognitive
decline.
New
incretin-based
peptide
in
a
long-acting
glucagon
(LY3324954),
GLP-1/glucagon
agonists
(survodutide,
pemvidutide,
mazdutide,
G49),
triple
GLP-1/GIP/glucagon
(retatrutide,
efocipegtrutide),
combination
amylin
analogue
cagrilintide
(CagriSema),
unimolecular
GLP-1/amylin
(amycretin),
GIP
antibody
agonism
(MariTide).
The
creation
multi-targeting
synthetic
peptides
provides
opportunities
management
type
2
obesity
as
well
new
therapeutic
approaches
an
expanding
list
associated
co-morbidities.
aim
review
is
acquaint
reader
developments
field
from
2023
present
(February
2025).
Frontiers in Neuroscience,
Journal Year:
2023,
Volume and Issue:
17
Published: Nov. 7, 2023
Enteroendocrine
cells
(EECs)
are
an
essential
interface
between
the
gut
and
brain
that
communicate
signals
about
nutrients,
pain,
even
information
from
our
microbiome.
EECs
hormone-producing
expressed
throughout
gastrointestinal
epithelium
have
been
leveraged
by
pharmaceuticals
like
semaglutide
(Ozempic,
Wegovy),
terzepatide
(Mounjaro),
retatrutide
(Phase
2)
for
diabetes
weight
control,
linaclotide
(Linzess)
to
treat
irritable
bowel
syndrome
(IBS)
visceral
pain.
This
review
focuses
on
role
of
intestinal
lumen
brain.
Canonically,
environment
through
a
variety
hormones,
dividing
into
separate
classes
based
hormone
each
cell
type
secretes.
Recent
studies
revealed
more
diverse
profiles
communication
modalities
including
direct
synaptic
with
peripheral
neurons.
known
as
neuropod
rapidly
relay
via
vagal
primary
sensory
Further,
this
discusses
complex
processing
machinery
within
EECs,
receptors
transduce
intraluminal
ion
channel
complement
govern
initiation
propagation
these
signals.
Deeper
understanding
EEC
physiology
is
necessary
safely
devastating
pervasive
conditions
obesity.
Pharmacology & Therapeutics,
Journal Year:
2024,
Volume and Issue:
255, P. 108589 - 108589
Published: Jan. 29, 2024
The
original
paradigm
of
classical
-
also
referred
to
as
canonical
cellular
signal
transduction
heterotrimeric
G
proteins
(G
protein)
is
defined
by
a
hierarchical,
orthograde
interaction
three
players:
the
agonist-activated
protein-coupled
receptor
(GPCR),
which
activates
transducing
protein,
that
in
turn
regulates
its
intracellular
effectors.
This
receptor-transducer-effector
concept
was
extended
identification
regulators
and
adapters
such
protein
signaling
(RGS),
kinases
like
βARK,
or
GPCR-interacting
arrestin
are
integrated
into
this
process
at
different
levels
enable
fine-tuning.
Finally,
atypical
mechanisms
regulators,
together
with
discovery
novel
modulators,
added
new
fascinating
dimension
transduction.
heterogeneous
group
accessory
modulators
coined
"activators
signaling"
(AGS)
plays
distinct
roles
non-canonical
pathways.
AGS
contribute
control
essential
functions
cell
development
division,
transport
processes,
secretion,
autophagy
movements.
As
such,
they
involved
numerous
biological
processes
crucial
for
diseases,
diabetes
mellitus,
cancer,
stroke,
represent
major
health
burdens.
Although
large
number
pathways
has
broadened
spectrum
communication
system,
their
underlying
mechanisms,
functions,
effects
poorly
understood.
In
review,
we
highlight
discuss
protein-dependent
focus
on
inhibitory
(Gi)
transduction,
review
recent
developments
open
questions,
address
potential
approaches
targeted
pharmacological
interventions.
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: Feb. 6, 2024
The
global
prevalence
of
diabetes
mellitus
(DM)
has
led
to
widespread
multi-system
damage,
especially
in
cardiovascular
and
renal
functions,
heightening
morbidity
mortality.
Emerging
antidiabetic
drugs
sodium-glucose
cotransporter
2
inhibitors
(SGLT2i),
glucagon-like
peptide-1
receptor
agonists
(GLP-1RAs),
dipeptidyl
peptidase-4
(DPP-4i)
have
demonstrated
efficacy
preserving
cardiac
function,
both
type
diabetic
non-diabetic
individuals.
To
understand
the
exact
impact
these
on
cardiorenal
protection
underlying
mechanisms,
we
conducted
a
comprehensive
review
recent
large-scale
clinical
trials
basic
research
focusing
SGLT2i,
GLP-1RAs,
DPP-4i.
Accumulating
evidence
highlights
diverse
mechanisms
including
glucose-dependent
independent
pathways,
revealing
their
potential
disease.
This
provides
critical
insights
into
protective
effects
DPP-4i
underscores
importance
medications
mitigating
progression
complications,
broader
implications
beyond
glycemic
management.
Journal of Endocrinology,
Journal Year:
2024,
Volume and Issue:
261(3)
Published: April 3, 2024
Adipose
tissue
was
once
known
as
a
reservoir
for
energy
storage
but
is
now
considered
crucial
organ
hormone
and
flux
with
important
effects
on
health
disease.
Glucose-dependent
insulinotropic
polypeptide
(GIP)
an
incretin
secreted
from
the
small
intestinal
K
cells,
responsible
augmenting
insulin
release,
has
gained
attention
its
independent
amicable
glucagon-like
peptide
1
(GLP-1),
another
L
cells.
The
GIP
receptor
(GIPR)
found
in
whole
adipose
tissue,
whereas
GLP-1
(GLP-1R)
not,
some
studies
suggest
that
GIPR
action
lowers
body
weight
plays
role
lipolysis,
glucose/lipid
uptake/disposal,
blood
flow,
lipid
oxidation,
free-fatty
acid
(FFA)
re-esterification,
which
may
or
not
be
influenced
by
other
hormones
such
insulin.
This
review
summarizes
research
of
(distinct
depots
white
brown)
using
cellular,
rodent,
human
models.
In
doing
so,
we
explore
mechanisms
GIPR-based
medications
treating
metabolic
disorders,
type
2
diabetes
obesity,
how
agonism
antagonism
contribute
to
improvements
outcomes,
potentially
through
actions
tissues.
FEBS Journal,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 19, 2024
Obesity
is
a
major
health
challenge
due
to
its
high
prevalence
and
associated
comorbidities.
The
excessive
intake
of
diet
rich
in
fat
sugars
leads
persistent
imbalance
between
energy
expenditure,
which
increases
adiposity.
Here,
we
provide
an
update
on
relevant
diet-microbe-host
interactions
contributing
or
protecting
from
obesity.
In
particular,
focus
how
unhealthy
diets
shape
the
gut
microbiota
thus
impact
crucial
intestinal
neuroendocrine
immune
system
functions.
We
describe
these
promote
dysfunction
gut-to-brain
pathways
involved
food
control
postprandial
metabolism
elevate
proinflammatory
tone,
promoting
obesity
metabolic
complications.
addition,
examples
this
knowledge
may
inspire
microbiome-based
interventions,
such
as
fecal
transplants,
probiotics,
biotherapeutics,
effectively
combat
obesity-related
disorders.
also
discuss
current
limitations
gaps
research
