Key
Takeaways
-
Prior
research
has
shown
that
diabetes
patients
have
a
higher
risk
of
active
TB,
while
people
with
obesity
have
increased
risks
for
serious
outcomes
following
an
infection. -
In
an
international
cohort
study
of
people
with
type
2
diabetes,
those
taking
a
GLP-1
drug
were
18%
to
51%
less
likely
to
develop
TB
compared
with
those
on
DPP-4
inhibitors,
sulfonylureas,
metformin,
and
SGLT2
inhibitors. -
Another
real-world
study
showed
that
diabetes
patients
on
the
GLP-1
agonist
tirzepatide
had
lower
risks
of
infection-related
mortality
and
hospitalization.
Recent
studies
suggest
that
people
with
type
2
diabetes
on
GLP-1
receptor
agonists
were
less
likely
to
develop
tuberculosis
(TB)
or
be
hospitalized
or
die
from
infections.
In
an
international
study
of
more
than
7
million
people,
type
2
diabetes
patients
taking
a
GLP-1
drug
were
less
likely
to
develop
TB
compared
with
those
on
other
antidiabetic
medications,
including
DPP-4
inhibitors
(HR
0.49,
95%
CI
0.43-0.56),
sulfonylureas
(HR
0.53,
95%
CI
0.47-0.59),
metformin
(HR
0.60,
95%
CI
0.51-0.70),
and
SGLT2
inhibitors
(HR
0.82,
95%
CI
0.72-0.92).
“These
findings
suggest
that
beyond
their
established
metabolic
benefits,
GLP-1
receptor
agonists
may
confer
additional
advantages
in
lowering
infection
risk,”
Chih-Cheng
Lai,
MD,
of
Chi
Mei
Medical
Center
in
Taiwan,
and
colleagues
concluded
in
Nature
Communications.
And
in
a
real-world
study
that
backed
the
major
adverse
cardiovascular
events
(MACE)
benefit
for
tirzepatide
(Mounjaro,
Zepbound),
the
GLP-1
drug
was
also
linked
with
protection
against
serious
infections.
Published
in
The
BMJ,
the
cohort
study
of
over
50,000
U.S.
adults
with
type
2
diabetes
and
atherosclerotic
cardiovascular
disease
found
that
tirzepatide
was
associated
with
substantially
lower
1-year
risks
for
various
infection
outcomes
compared
with
sitagliptin
(Janumet),
a
DPP-4
inhibitor:
-
Infection-related
mortality:
HR
0.40
(95%
CI
0.26-0.61) -
Infection-related
hospitalization:
HR
0.64
(95%
CI
0.55-0.75) -
Urinary
tract
infections:
HR
0.83
(95%
CI
0.76-0.91) -
Infections
in
any
care
setting:
HR
0.83
(95%
CI
0.78-0.87)
A
reduction
in
all-cause
mortality
among
the
tirzepatide
users
was
also
observed
in
the
study
from
researchers
led
by
Nils
Krüger,
MD,
of
Harvard
Medical
School
in
Boston.
“One
plausible
explanation
that
our
study
supports
is
the
substantial
reduction
in
serious
bacterial
infections
observed
among
individuals
who
initiated
tirzepatide,
suggesting
that
part
of
the
survival
benefit
may
reflect
effects
beyond
atherosclerotic
mechanisms,”
wrote
Krüger
and
colleagues.
Together,
the
two
studies
lend
support
to
a
recent
umbrella
review
that
turned
up
convincing
evidence
that
GLP-1
medications
had
protective
associations
against
infection-related
outcomes,
especially
for
serious
infections.
People
with
diabetes
have
an
increased
risk
for
active
TB
and
worse
subsequent
outcomes,
according
to
the
CDC.
And
past
research
has
suggested
that
obesity
may
be
responsible
for
1
in
10
infection-related
deaths
in
adults.
Obesity’s
ties
to
increased
systemic
inflammation,
immune
system
dysfunction,
and
metabolic
disturbances
likely
help
drive
that
association.
Based
on
preclinical
and
translational
data,
Lai
and
co-authors
suggested
that
GLP-1
drugs
could
influence
people’s
susceptibility
to
infections
and
outperform
other
classes
of
antidiabetics
at
lower
infection
risk.
“In
obese,
high-fat
diet-induced
diabetic
mice,
GLP-1RA
[receptor
agonists]
outperformed
insulin
in
restoring
host
defense
against
infection
by
enhancing
neutrophil
phagocytosis,
migration,
and
bacterial
clearance,”
they
wrote.
“Prolonged
GLP-1RA
treatment
further
improved
infection
resistance
by
correcting
hyperglycemia,
increasing
neutrophil
counts,
and
restoring
innate
immune
competence,”
added
Lai
and
colleagues.
“These
improvements
indicate
that
GLP-1RA
may
provide
a
superior
anti-infective
effect
compared
with
conventional
therapy,
not
only
through
glycemic
control
but
also
by
directly
enhancing
immune
cell
function.”
Beyond
their
long-proven
benefits
for
type
2
diabetes
and
obesity,
GLP-1
drugs
such
as
tirzepatide
and
semaglutide
(Ozempic,
Wegovy)
have
garnered
a
growing
number
of
FDA-approved
indications
for
conditions
including
chronic
kidney
disease,
sleep
apnea,
and
metabolic
dysfunction-associated
steatohepatitis,
and
to
reduce
the
risk
for
MACE.
And
observational
and
small
randomized
studies
have
suggested
other
potential
benefits
as
well,
including
cancer
risk
or
recurrence
reduction
and
for
people
with
addictions
to
alcohol
or
opioids.
Study
Details
For
the
TB
study,
the
investigators
drew
on
2017
to
2025
data
from
the
TriNetX
international
health
research
network.
After
adjustment,
baseline
characteristics
—
such
as
age,
sex,
race,
HbA1c,
body
mass
index,
and
comorbidities
—
were
well
balanced
within
each
cohort,
which
were
divided
up
by
antidiabetic
medication
class.
Limitations
included
a
lack
of
data
on
key
clinically
relevant
TB
variables,
limiting
analysis
of
GLP-1
receptor
agonists
effects
across
TB
exposure
patterns
and
disease
phenotypes.
In
addition,
substantial
variation
in
TB
epidemiology
across
countries
could
have
introduced
geographical
confounding.
In
the
MACE
study,
the
researchers
analyzed
data
from
two
U.S.
administrative
claims
databases
from
2022
to
2025
on
adults
40
and
over
with
type
2
diabetes
and
atherosclerotic
cardiovascular
disease.
Median
patient
age
was
70
years,
51%
were
women,
and
85%
took
statins.
Limitations
included
the
relatively
short
follow-up
period,
which
could
underestimate
long-term
cardiovascular
and
safety
effects.
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