A systematic review of the effect of oral

glucocorticoids on
energy intake, appetite, and body weight in humans

Journal reading

dr. Achmad Zainudin Arif*

dr. Laksmi Sasiarini, SpPD-KEMD**
* Mahasiswa Program Pendidikan Dokter Spesialis Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Brawijaya
** Staf Divisi Endokrin Bagian Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Brawijaya

Introduction
Obesity is a major risk factor for
many serious and debilitating chronic
diseases.
Oral glucocorticoids (OCS) are
considered to have obesogenic
effects
Dose-response relationship ?
Associated risks can be
communicated to patients
recommendation

Introduction
short and long terms anti-inflammatory
properties
asthma, rheumatologic diseases, dermatological
disorders, autoimmune diseases, other
inflammatory disorders

adverse effects :
dose dependent
half-life
Frequency
time of day administered
route of administration of the drugs

Oral glucocorticoid adverse

effect
Short-term :
insomnia, constipation, bloating, mood changes, and
hyperglycemia

long-term :
Osteoporosis
bone necrosis
arterial hypertension
Diabetes
hypothalamic-pituitary-adrenal axis suppression,
Cushing syndrome
Cataracts
Glaucoma
Skin thinning, easy bruising
muscle atrophy

Introduction
Common OCS adverse effect :
Increase body weight (BW) and appetite : in cancer
patient, dialysis patient

OCS adverse effects not often reported

recall and self-reported by subjects post
intervention
Bias toward reporting adverse effects following
long-term rather than short-term interventions
Adverse effects are not investigated as primary
outcomes in OCS intervention studies

Objective
To identify clinically significant effect
sizes including energy intake
changes of greater than or equal to
2 MJ/d and a 5% change in BW and
whether a relationship exists
between glucocorticoid dose,
duration, and effect size in
subjects with inflammatory
conditions and healthy subjects

Inclusion

Exclution

Inclusion

Inclusion

Analysis
Objective evidence demonstrating that
glucocorticoids have an impact on BW,
energy intake, or appetite is limited.
short-term OCS use is unlikely to lead to
increased energy intake, although they
may increase energy expenditure BW
was not significantly increased
long-term OCS use clinically significant
increases in BW increase in total body
water

Analysis
glucocorticoids do not have a
significant impact on fat and lean
mass in treatment periods lasting 7
days or less
The long-term studies included in the
review did not examine effects on
body composition

Analysis
Weight gain and obesity occur as a
result of energy imbalance where
greater kilojoules are consumed than
are expended.
Increased energy intake generally
precedes weight gain and obesity as
the consequence of an increased
appetite.

Analysis
Body composition changes such as the
redistribution and accumulation of fat in
the face and dorsocervical region
leading to appearance of a moon face
and buffalo hump known as
lipodystrophy have been reported after
longterm use (>3 months) in subjects
with inflammatory conditions, dialysis
patients, and after organ transplantation

Analysis
Some research suggest that the metabolic
effects of glucocorticoids are dose
dependent, with low doses exhibiting
anabolic effects and high doses producing
catabolic effects, associated with
decreased BW and food intake
OCS :
stimulate appetite and dietary intake at low
doses
inhibit appetite at high doses

Analysis
Future studies that measure BW as
an outcome of OCS therapy should
measure dietary intake using
appropriate dietary assessment
tools, such as food records, and also
measure physical activity, as both
are confounders of weight change.

Study Limitation
Diversity of numerous features of the
studies under investigation
study populations, aims, study design, and
outcome variables

Changes in BW without measuring energy

intake, physical activity, and energy
metabolism.
Measurement of impact of fluid
distribution on BW changes not
considered.

Study Limitation
there is insufficient objective
evidence to conclude that short term
use of OCS causes clinically
significant changes in energy intake,
BW, body composition, or appetite in
healthy controls or subjects with
inflammatory conditions

Conclusion
long-term use of OCS may contribute
to clinically significant increases in
BW
Further studies are needed in a range
of patient populations to elucidate
the effects of OCS on energy intake
and expenditure, BW, and appetite
with validated, sensitive tools, in
well-designed and adequately
powered RCTs.

Criticall Appraisal
Stateme
nt 1.1

The study addresses a clearly defined research question

Obesity is a major risk

Always
factor for many serious
applies.
and debilitating chronic
diseases.
Oral glucocorticoids (OCS)
are considered to have
obesogenic effects
Dose-response relationship
?

Why is this important?

When
Response:
does this
statement
apply?
Yes. Where the research question is
clearly stated. Reference to a protocol,
ethics approval, or pre-determined/a
priori published research objectives may
meet this criterion.

Criticall Appraisal
Statem
ent 1.2

At least two people should select studies and extract data

What
does
statement mean?

this When
does this
stateme
nt apply?
While extracting data
Always
from studies may be
applies.
an objective process,
there is always scope
for error or
misinterpretation.
Having two or more
people carry out data
extraction
independently of each
other reduces the risk
of error or bias
creeping in. There
should also be a clear
mechanism for arriving
at consensus where

Response:

Yes. The study clearly states that

two or more people were involved
in data extraction, and that they
were working independently of
each other. A method of reaching
consensus is also described.

Criticall Appraisal
Statement
1.3

A comprehensive literature search is carried out

A systematic review must, by

definition, include a
comprehensive literature
search covering all likely
sources of studies. Definition
of comprehensive is difficult
as a numer of factors
influence the scope of a
search. As a minimum at least
two major electronic
databases should be
searched. Major databases
include the Cochrane library,
Embase, and Medline. Some
subjects should involve more
specialized databases such as
AMED, CINAHL.

What does
mean?

this

statement When does

this
statement
apply?
Almost
always.

Response:

Yes. full details of the literature search are

provided either in the review itself or in a
separate source that is available to those
evaluating the review (eg in an online
supplement).
Only english article included

Criticall Appraisal
Statem
ent 1.4

The authors clearly state if or

publication type
What
does
this When
statement mean?
does this
stateme
nt
apply?
This comes back to
Always
inclusion / exclusion
applies.
criteria. Authors will
normally have a range
of clinical criteria to
consider, but may
decide to impose
additional limitations
Common limitations
are study type,
language of
publication, and
published or
unpublished literature.

how they limited their review by

Response:

Yes. All criteria used to select

studies are clearly specified..

Criticall Appraisal
Statem
ent 1.5

The included and excluded studies are listed

What does this
statement mean?

When
Response:
does this
stateme
nt
apply?
A list of included and Always
Yes. Studies included in the
excluded
studies applies. review, or excluded following
should be provided.
application of the agreed exclusion
criteria, are listed.

Criticall Appraisal
Stateme
nt 1.6

The characteristics of the included studies are provided

In an aggregated form
Always
such as a table, data from applies.
the original studies should
be provided on the
participants, interventions
and outcomes. The
ranges of characteristics
in all the studies analyzed
e.g., age, race, sex,
relevant socioeconomic
data, disease status,
duration, severity, or
other diseases should be
reported.

What does this statement

mean?

When
does this
statemen
t apply?

Score should be:

Yes. data from the original studies is

provided in sufficient detail to allow
assessment of the comparability of the
study populations. Note that a format
other than a table is acceptable, as
long as the information noted here is
provided.

Criticall Appraisal
Stateme
nt 1.7

The methodological quality of the included studies

documented
What does this statement When
Response:
mean?
does this
statemen
t apply?

This is effectively asking

Always
whether the authors
applies.
appraised the individual
studies in a similar way to
how you are appraising
the review.

is

assessed

and

Yes. The authors report the appraisal of

individual studies using level of
evidence.

Criticall Appraisal
Stateme
nt 1.8

The scientific quality of the included studies was assessed appropriately

What does this statement
mean?

When
does this
statemen
t apply?

Response:

The methodological rigor

and scientific quality of
the individual papers
should be considered in
the analysis and the
conclusions of the review,
and explicitly stated in
formulating
recommendations.

Always
applies

Yes. The review includes information on

individual study quality along with
outcome data and conclusions from
each study.

Criticall Appraisal
Statement
1.9

Appropriate methods are used to combine the individual study findings

For the pooled results, a test Always

should be done to ensure the applies
studies were combinable, to
assess their homogeneity (eg
-squared
test).
If
heterogeneity exists a random
effects model should be used
and/or
the
clinical
appropriateness of combining
should
be
taken
into
consideration (ie is it sensible
to combine?). Indicate yes
where the authors mention or
describe
heterogeneity
or
variability between results and
discuss the consequences (eg
where authors declare they
cannot pool results because of
heterogeneity).

What does this statement

mean?

When does
this
statement
apply?

Response:

Yes. The authors mention or describe

heterogeneity or variability between results.
Also where authors declare they cannot pool
results because of heterogeneity.

Criticall Appraisal
Stateme
nt 1.10

The likelihood of publication bias is assessed

It is always possible for Always

publication bias to exist, applies
but it cannot be proved or
disproved absolutely. A
good
review
should
nevertheless take account
of the possibility that it
may be present. An
assessment of publication
bias should include a
combination of graphical
aids (eg funnel plot, other
available tests) and/or
statistical tests (eg Egger
regression test, HedgesOlken test).

What does this statement

mean?

When
does this
statemen
t apply?

Response:

Cant tell. no comment on the risk of

publication bias is made.

Criticall Appraisal
Statem
ent
1.11

Conflicts of interest are declared.

What does this
statement mean?

When
Response:
does this
stateme
nt
apply?
Any financial or other Always
No. Where there is no discussion
relevant interests of applies. of sources of support.
the review authors
should be reported,
along
with
any
financial
support
provided
for
the
conduct of the review.
Ideally, that authors
should also report on
the
funding
of
individual
studies
included in the review.