RINGKASAN KASUS PPK

Seorang wanita umur 67 tahun dengan hipertensi dan obesitas datang ke

dokter puskesmas untuk mengontrol tekanan darahnya karena merasa
nyeri kepala dan pusing. Pasien tidak merasakan gejala klinis DM, hanya
ditemukan poliuri dan lemah di kaki. Karena ada program dokter keluarga,
maka wanita tersebut mengecek gula darah sewaktu dan hasilnya 232
mg/dL. Dokter memberikan obat berupa Adalat (nifedipi, obat
antihipertensi), glibenklamid, metformin, dan glukodex.
The Well-Built, Patient-Oriented Clinical Question
Question Component
P-Patien or Population

I-Intervention

C-Comparison
O-Outcome

Your Question
Siapakah yang diteliti?
Pasien nondiabetes dengan umur
>25 tahun, IMT 24 atau lebih (22
untuk asia), KGD 95-125 mg/dl dan
140-199 mg/dl setelah 2 jam
menerima 75 g glukosa oral.
Obat apa yang diberikan dalam
penelitian?
Metformin 850 mg 2x/hari
Apa pembandingnya?
Perbaikan pola gaya hidup
Apa saja hasil yang diharapkan?
Perbaikan gaya hidup dan
metformin menurunkan kejadian
diabetes pada orang dengan risiko
tinggi

The well-built clinical question :

Terapi mana yang lebih baik antara perubahan gaya hidup dan metformin
untuk menurunkan angka kejadian DM type 2 pada orang dengan risiko
tinggi?
Type of
Question

Ideal Type of Study

Therapy

RCT

Prevention

RCT > Cohort Study > Case Control

Diagnosis

Prospective, blind controlled trial comparison to gold

standard

 Prognosis

Cohort Study > Case Control > Case Series/Case

Report

Etiology/Harm

RCT > Cohort Study > Case Control

Cost analysis

economic analysis

Note: Meta-analyses and systematic reviews, when available,

often provide the best answers
to clinical questions.

Search Strategy Development

Primary search term

Nondiabetic namun resiko
tinggi DM tipe 2
Metformin

Life style intervention

Menurunkan angka kejadian DM

Synonym 1

Synonym 2

CONSORT CHECKLIST
Section
and Topic

Title and
Abstract

Ite
m
No.

Descriptor

How participants
were allocated to
interventions (e.g.,
"random allocation",
"randomized", or
"randomly
assigned").

Report
ed on
Page
No.
393

Content

Dalam jurnal disebutkan

bahwa
metode
yang
digunakan
adalah
dengan
mengambil
pasien
nondiabetik
secara acak.
Methods We randomly
assigned
3234
nondiabetic persons with
elevated
fasting
and
post-load
plasma
glucose concentrations

to placebo,
(850)
INTRODU
CTION
Backgroun
d

Scientific
background and
explanation of
rationale.

393

metformin

Dalam jurnal djelaskan

bahwa diabetes tipe 2
adalah penyakit yang
mahal dan serius yang
menyerang kira-kira 8%
dari orang tua di
Amerika.
Diabetes mellitus,
formerly called noninsulin-dependent
diabetes mellitus, is a
serious, costly disease
affecting approximately
8 percent of adults in the
United States.

METHODS
3
Participant
s

Eligibility criteria for

participants and the
settings and
locations where the
data were collected.

394

Diambil dari 27 pusat

klinik. Kriteria yang
dimasukkan dalam
penelitian adalah orang
yang berusia lebih dari
25 tahun dengan IMT 24
atau lebih (22 atau lebih
untuk orang Asia) dan
konsentrasi glukosa
plasma puasa 95-125
mg/dL ( < 125 mg/dL
pada orang Amerika
Indian) dan 140-199
mg/dL 2 jam setelah
diberikan 75 g glukosa
oral.
We conducted a clinical
trial involving persons at
27 centers
who were at high risk for
diabetes. Eligibility

criteria included an
age of at least 25
years, a bodymass
index (the weight in
kilograms divided by the
square of the height in
meters) of 24 or higher
(22 or higher in Asians),
and a plasma glucose
concentration of 95 to
125 mg per deciliter
(5.3 to 6.9 mmol per
liter) in the fasting state
(125 mg per deciliter in
the American Indian
clinics) and 140 to 199
mg per deciliter (7.8 to
11.0 mmol per liter) two
hours after a 75-g oral
glucose load.
Interventio
ns

Precise details of
the interventions
intended for each
group and how and
when they were
actually
administered.

394

Di dalam jurnal
dijelaskan bahwa ada 3
pelakuan: gaya hidup
standar ditambah
metformin (Glucophage)
dengan dosis 2 x 850
mg, gaya hidup standar
ditambah plasebo 2 x
sehari, atau program
intensif modifikasi gaya
hidup.
Participants were
randomly assigned to
one of three
interventions:
standard lifestyle
recommendations
plus metformin
(Glucophage) at a dose

of 850 mg twice daily,

standard lifestyle
recommendations
plus placebo twice
daily, or an intensive
program of lifestyle
modification.
Objectives

Outcomes

Specific objectives
and hypotheses.

Clearly defined
primary and
secondary outcome
measures and,
when applicable,
any methods used
to enhance the
quality of
measurements
(e.g., multiple
observations,
training of
assessors).

393

394

Di dalam jurnal
dijelaskan bahwa
mereka menghipotesis
dengan memodifikasi
gaya hidup atau dengan
pemberian metformin
akan mencegah atau
memperlambat
perkembangan diabetes.
We hypothesized that
modifying these
factors with a
lifestyle-intervention
program or the
administration of
metformin would
prevent or delay the
development of
diabetes.
Dalam jurnal dijelaskan
bahwa primary outcome
untuk diagnosis diabetes
dilakukan TTGO atau yang
secondary nya dengan
gula darah puasa menurut
kriteria ADA tahun 1997.

The primary outcome

was diabetes, diagnosed
on the basis of an annual
oral glucose-tolerance
test or a semiannual
fasting plasma glucose

test, according to the

1997 criteria of the
American Diabetes
Association: a value for
plasma glucose of 126
mg per deciliter (7.0
mmol per liter) or higher
in the fasting state or
200 mg per
deciliter (11.1 mmol per
liter) or higher two hours
after a 75-g oral glucose
load.
The secondary: In
addition to the
semiannual
measurements, fasting
plasma glucose was
measured if symptoms
suggestive of diabetes
developed.
Sample
size

How sample size

was determined
and, when
applicable,
explanation of any
interim analyses
and stopping rules.

394

Di
dalam
jurnal
dijelaskan bahwa yang
mengikuti
peneliatian
adalah
oarang
yang
lebih dari 25 tahun yang
memenuhi kriteria. Jika
orang tersebut sedang
mengkonsumsi
obat
yang dapat mengubah
toleransi glukosa atau
sedang
sakit
yang
harapan
hidupnya
rendah
maka
orang
tersebut tidak masuk
kriteria

Eligibility
criteria
included an age of at
least
25
years,
a

bodymass Index (the

weight
in
kilograms
divided by the square of
the height in meters) of
24 or higher (22 or
higher in Asians), and a
plasma
glucose
concentration of 95 to
125 mg per deciliter (5.3
to 6.9 mmol per liter) in
the fasting state (125
mg per deciliter in the
American Indian clinics)
and140 to 199 mg per
deciliter (7.8 to 11.0
mmol per liter) two
hours after a 75-g oral
glucose
load.
These
concentrations
are
elevated but are not
diagnostic of diabetes
according to the 1997
criteria of the American
Diabetes
Association.
Before June 1997, the
criterion
for
plasma
glucose in the fasting
state was 100 to 139 mg
per deciliter (5.6 to 7.7
mmol per liter), or 139
mg per deciliter in the
American Indian clinics.
Eligible persons were
excluded if they were
taking medicines known
to
alter
glucose
tolerance or if they had
illnesses
that
could
seriously reduce their
life expectancy or their
ability to participate in

the trial. Recruitment

was designed to enroll
approximately half the
participants from racial
or
ethnic
minority
groups.
A
four-step
screening
and
recruitment process was
developed to identify
eligible participants.
Randomiza
tion -Sequence
generation

Randomiza
tion -Allocation
concealme
nt

Randomiza
tion -Implement
ation

10

Method used to
generate the
random allocation
sequence, including
details of any
restriction (eg:
blocking,
stratification)
Method used to
implement the
random allocation
sequence (e.g.,
numbered
containers or
central telephone),
clarifying whether
the sequence was
concealed until
interventions were
assigned.
Who generated the
allocation
sequence, who
enrolled
participants, and
who assigned
participants to their
groups.

Di dalam
dijelaskan

jurnal

tidak

Di dalam
dijelaskan

jurnal

tidak

393
The Diabetes
Prevention Program
Research Group
conducted a large,
randomized clinical trial
involving adults in the
United States who were
at high risk for the
development of type 2
diabetes.

Blinding
(masking)

Statistical
methods

Result
Participant

11

Whether or not
participants, those
administering the
interventions, and
those assessing the
outcomes were
blinded to group
assignment. If done,
how the success of
blinding was
evaluated.

394

12

Statistical methods
used to compare
groups for primary
outcome(s);
Methods for
additional analyses,
such as subgroup
analyses and
adjusted analyses.

394

13

Flow of participant

395

Di
dalam
jurnal
dijelaskan bahwa antara
pemberian
metformin
dan plasebo, keduanya
dibutakan.
Assignments
to
metformin and placebo
were double-blinded.
The blinded
treatment phase was
terminated one year
early, in May 2001, on
the advice of the data
monitoring board, on the
basis of data obtained
through March 31, 2001,
the closing date for this
report.
Dalam jurnal dijelaskan
bahwa pelakuan secara
acak diambil dari klinik
pusat. Harga nilai P (tak
berubah)
Random treatment
assignments
were
stratified according to
the
clinical
center.
Assignments
to
metformin and placebo
were
double-blinded.
The study design and
analysis followed the
intenion-to-treat
principle.
Nominal
(unadjusted) P values
and confidence intervals
are reported.

Dalam jurnal dijelaskan

flow

Recruitme
nt

Baseline
data

14

15

through each stage

(a diagram is
strongly
recommended).
Specifically, for
each group report
the number of
participant
randomly assigned,
receiving intended
treatment,
completing the
study protocol, and
analyzed for the
primary outcome.
Discribe protocol
deviations from
study planned,
together with
reasons.
Dates defining the
periods of
recruitment and
follow up.

Baseline
demographic and
clinical

pasrtisipan
yang
mengikuti penelitian ini
dan tersaji dalan tabel 1.

395

395

Dalam jurnal dijelaskan

bahwa pengumpulan
partisipan dilakukan dari
tahun 1996 sampai
1999.
From 1996 to 1999,
we randomly assigned
3234 study participants
to one of the three
interventions (1082 to
placebo, 1073 to
metformin, and 1079 to
the intensive lifestyle
intervention).
The participants were
followed for an
average of 2.8 years
Data diambil dari orang
mempunyai risiko tinggi
DM dan dimasukkan ke

characteristics of
ech group.

dalam 3 study group.

Base-line
characteristics, including
all measured risk factors
for diabetes, were
similar among the three
study groups (Table 1).

Number
analyzed

Outcomes
and
estimation

16

17

Number of
participant
(denominator) in
eah group included
in each analysis and
whether the
analysis was by
intention to
treat. State the
result in absolut
number as when
feasible (eg, 10/20,
not 50%)

395

For each primary

and secondary
outcome, a
summary of result
for aech group, and
the estimated effect
and its precision
(eg, 95% convident
interval).

397

Dalam jurnal disebutkan

bahwa yang mengikuti
penelitian ini ada 3234
orang
From 1996 to 1999, we
randomly assigned 3234
study participants to one
of the three
interventions
(1082 to placebo, 1073
to metformin, and 1079
to the intensive lifestyle
intervention).
Dalam jurnal dijelaskan
bahwa mereka
memperkirakan insidensi
DM dalam 3 tahun
adalah 28,9% untuk
pemberian plasebo,
21,7% metformin, dan
14,4% untuk modifikasi
gaya hidup.

Ancillary
analyses

18

Adverse
event

19

Adress multiplicity
by reporting any
other analyses
peformed, including
sub group analyses
and adjusted
analyses, indicating
those prespecipied
and those
exploratory.
All important
adverse events or
side effects in each
intervention group.

397 &
401

"The estimated
cumulative
incidence of diabetes at
three years was 28.9
percent, 21.7 percent,
and 14.4 percent in the
placebo, metformin, and
lifestyle-intervention
groups, respectively.
On the basis of these
rates, the estimated
number of persons who
would need to be treated
for three
years to prevent one
case of diabetes during
this period is 6.9 (95
percent confidence
interval, 5.4 to 9.5) for
the lifestyle intervention
and 13.9 (95 percent
confidence interval, 8.7
to 33.9) for metformin.
Di dalam jurnal tidak
dijelaskan

Efek
samping
yang
ditimbulkan
dari
penggunaan metformin
adalah
gangguan
gastrointestinal berupa
diare,
kentut,
mual
muntah. Sedangkan dari

grup modifikasi gaya

hidup
adalah
muskuloskeletal
simptom berupa mialgia,
artriris, atau atralgia.

Comment
Interpretati
on

Generalizab
ility

20

21

Interpretations of
the result, taking
into account study
hypotheses, sources
of potential bias or
imprecision, and
outcomes.

Generalizability
(external validity) of
the trial findings.

398

399

Dalam jurnal dijelaskan

bahwa hipotesis awal
sejalan dengan hasil dari
penelitian yaitu DM tipe
2 dapat dicegah atau
dihambat
pertumbuhannya
pada
seseorang dengan risiko
tinggi.
Our results support the
hypothesis that type 2
dibetes can be
prevented or delayed in
persons at high risk for
the disease.
Di
dalam
jurnal
dijelaskan
bahwa
penelitian
sebelumnya
tidak
menjelaskan
bahwa
obat
untuk
diabetes efektif untuk
pencegahan,
mungkin
karena sampel kecil dan
data kurang

Overall
evidence

22

General
interpretation of the
result in the context
of current evidence.

401

Previous studies have

not demonstrated that
drugs used to treat
diabetes are effective for
its prevention, perhaps
because of small
samples and the lack of
data on adherence to
the prescribed regimens.
In contrast, metformin
was effective in our
study, althoughless so
than the lifestyle
intervention.
Dalam jurnal dijelaskan
pemberian
metformin
dan
modifikasi
gaya
hidup 2 kali lebih efektif
dalam menunda dan
pencegahan DM tipe 2.
In summary, our study
showed that treatment
with
metformin
and
modification of lifestyle
were two highly effective
means of delaying or
preventing
type
2
diabetes. The lifestyle
interventions
was
particularly
effective,
with
one
case
of
diabetes prevented per
seven persons treated
for three years. Thus, it
should also be possible
to delay or prevent the
development
of
complications,
substantially
reducing

the individual and public

health
burden
of
diabetes.
THERAPY WORKSHEET
Is the research valid?
1a. Was the assignment of
patients randomised?

1b. Was the randomisation list

concealed?
1c. Were subjects and
clinicians blind to which
treatment was being
received?
2a. Were all subjects who
entered the trial accounted
for at its conclution?

2b. Were they analysed in the

groups to which they were
randomised?

( ) Yes

( ) Yes
( ) Yes

( ) Yes

( ) Yes

Comments
1a. Pasien diambil secara
acak dari 27 pusat klinik
dengan mengambil 3234
pasien nondiabetik namun
risiko tinggi DM.
1b. Pengacakan tidak
dilakukan secara sembunyi.
1c. Antara subjek dan peneliti
dibutakan.
2a.
Semua
partisipan
diperhitungkan dalam hasil
yaitu berjumlah 3234 orang
dengan rincian plasebo 1082,
metformin 1073, dan gaya
hidup 1079
2b. Diambil dari 27 pusat
klinik secara acak sebanyak
3234 orang dengan kriteria
yang memenuhi.
Sesuai dengan tabel 1

3a. Aside from the

experimental treatment, were
the groups treated aqually?
3b. Were the groups similar at
the start of the trial?

( ) No
( ) Yes

3a. Di dalam
disebutkan

jurnal

tidak

3b. Dari awal sampai akhir

penelitian berjumlah 3234
orang dan sebanyak 99,6%
masih hidup.