Once-Weekly Exenatide Versus

Once- or Twice-Daily Insulin

Detemir
Pembimbing :
Dr. Daril! "#. Pd.

Penyusun:
$esa %usuma &'()*''+''+,-
Randomized, open-label, clinical trial of efcacy and safety in patients with type 2
diabetes treated with metformin alone or in combination with sulfonylureas
Latar Belakang

Diabetes tipe-2 berhubungan dengan masalah obesitas

dan membutukan banyak interensi untuk mencapai
target !"# dalam $angka pan$ang pan$ang

%erapi untuk memperbaiki gula darah dan berat badan

tanpa resiko efek hipoglikemi dan penambahan berat
badan&
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.

-asien yang tidak mencapai kontrol gula yang cukup

dengan oral anti diabetes drugs . *!Ds / membutuhkan
tambahan terapi untuk mencapai target !"# 0 1,23
.lucagon-like #e#tide
&./P--) rece#tor agonist
&Exenatide-
Insulin detemir
Latar Belakang
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.

meningkatknya efek incretin meransang

ker$a pankreas untuk memproduksi lebih
banyak insulin sebagai respon
hiperglikemia&

4L--" $uga dapat memperbaiki dan

meningkatkan fungsi pankreas karena
mempunyai efek menghambat apoptosis
dan bahkan merangsang neogenesis
serta proliferasi sel beta&

4L--" hanya akan merangsang

pankreas bila ter$adi hiperglikemia
.glucose dependent manner / sehingga
peningkatan efek 4L--" tidak akan
menimbulkan risiko hipoglikemia&

5fek incretin terhadap saluran cerna

$uga dianggap menguntungkan karena
bersifat netral bahkan dapat
menurunkan berat badan&

%erapi insulin basal analog yang

memiliki ker$a pan$ang umumnya
digunakan sebagai pilihan awal
terapi insulin&

6nsulin detemir dan glargine lebih

dian$urkan, dibanding insulin-insulin
7-(& )ebab insulin-insulin itu
memiliki puncak ker$a yang relatif
rendah dan efeknya lebi konsisten
sepan$ang hari&

Dibandingkan dengan regimen basal

insulin lain/, insulin detemir
memberikan efek kontrol glukosa yang
sama, namun dengan efek
penambahan berat badan dan resiko
hipoglikemia yang lebih sedikit&
.lucagon-like #e#tide
&./P--) rece#tor agonist
&Exenatide-
Insulin detemir
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.
%u$uan -enelitian

'embandingan hasil penggunaan 5+enatide

dan 6nsulin Detemir berupa kontrol gula darah,
resiko kardioaskular, keamanan, dan
tolerabilitas pada pasien diabetes melitus tipe 2
yang tidak terkontrol dengan obat anti diabetes
oral&
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.
Design dan 'etode -enelitian
Desain )tudi

)tudy %ype , 6nterentional

)tudy Design ,

!llocation , Randomized 5nd point

#lassification , )afety8 5fficacy )tudy

6nterention

'odel , -arallel !ssignment

'asking , *pen Label

-rimary -urpose , %reatment

Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.
Design dan 'etode -enelitian

*b$ek , 222
-asien diabetes yang tidak terkontrol glukosadarahnya
dengan terapi metformin atau kombinasi metformin dan sulfonilurea/
)tudi -opulasi
Design dan 'etode -enelitian
)tudi -opulasi
%
0
I
T
E
0
I
1
I
n
%
/
2
"
i
.ender /aki-laki3#erem#uan
9mur : "; th
!"# leel <=& " - >"?& ?3
. <2@ - >;1 mmol8mol/
B'6 22 kg8m
2
- @2 kg8m2
)edang mengkonsumsi metformin dengan dosis stabil <"??? mg dalam
minimum A bulan terakhir
!tau
)edang mengkonsumsi metformin dengan dosis <"??? mg dan sulfonilurea
.dalam obat terpisah8 bukan kombinasi dosis/ dalam minimum A bulan terakhir&
%
0
I
T
E
0
I
1
E
%
"
%
/
2
"
I
-unya kontraindikasi dengan *!D yang digunakan&
-unya alergi atau hipersensitiitas terhadap insulin detemir, ecenatide atau substansi yang terkandung
didalamnya&
Dalam terapi @ minggu screening glukokortikoid sistemik .oral, intraena, atau intramuskular/ atau
dalam terapi teratur inhaled intranasal steroid yang diketahui punya tingkat absorpsi sistemik yang
tinggi&
Dalam terapi glukokortikoid untuk defisiensi hipopituitari kortikotropik .penyakit addison/
Dalam terapi obat yang dapat menurunkan berat badan dalam A bulan penelitian&
-ernah :A kali episode hipoglikemi mayor dalam 1 bulan terakhir&
-ernah terapi .selama :2 minggu dalam waktu A bulan sebelum skrining/,
6nsulin, alpha-glucosidase, ByettaB .e+enatide B6D formulation/, thiazolidinediones .%CD/, dipeptidyl
peptidase .D--/-@ inhibitors

)ebelumnya pernah selesai atau ikut dalam studi inestigasi e+enatide
-ernah menerima terapi obat yang tidak menerima regulatory approal indikasi apapun .dalam A?
hari terakhir/
)edang dalam atau berhenti .dalam A? hari terakhir/ dari clinical trial inestigasi obat8 tipe penelitian
medis
Design dan 'etode -enelitian
)tudi -opulasi
Ratio ","

%anggal studi dimulai , *ctober 2??D

%anggal studi selesai , December 2?""

Priar! Co"letion Date , Euly 2?""

Exenatide Insulin Detemir
6n$eksi subkutan ,
2 mg, "+8minggu
6n$eksi subkutan
Dg dosis titrasi, 2+8 hari
6nterensi
Design dan 'etode -enelitian
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.

)elf monitored glukosa darah di awal dan antara minggu "; dan
21&

Blood samples diambil saat awal dan minggu ke 21 untuk

mengukur, !"#, F-4, fasting plasma lipids, dan marker
kardioaskular&

Berat badan, waist circumference, dan ital sign diukur pada setiap
studi isit&

)etiap epidose hipoglikemia 8 efek samping lain, dicatat .durasi,

timing, ntensitas, dan faktor lain dari ge$ala/ lewat alat komunikasi,
isit dan ealuation Guestionnaire&

-enilaian kualitas hidup menggunakan %he -sychological 4eneral

Helll Being inde+ and 6mpact of Height on Iuality of Life-Lite&
6nterensi
Design dan 'etode -enelitian
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.

-imary J 'enghitung proporsi pasien yang mencapai

!"# >=&? 3 .2A mmol8mol/ with BB loss < "&? Kg pada akhir
penelitian&

)econdary J 'enghitung proporsi pasien yang mencapai

!"# >=&@ 3 .2= mmol8mol/ with BB loss < "&? Kg
!"# >=&? 3 .2A mmol8mol/ with BB loss > "&? Kg
!"# >=&@ 3 .2= mmol8mol/
!"# >=&? 3 .2A mmol8mol/
!"# >1&2 3 .@; mmol8mol/
.dari baseline L end point, baseline L minggu ke "2, ";, 21/
outcomes
Design dan 'etode -enelitian
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.

-erubahan F-4 dan Resiko parameter

kardioaskular .B'6, waist circumference,
%ekanan darak sistolik diastolik, (eart rate,
lipids profile, plasminogen actiator inhi bitor-"
.-!6-"/, high-sensitiity #- reactie protein .hs-
#R-/, and adiponectindari baseline-end point&

!danya efek samping

Design dan 'etode -enelitian
outcomes
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.
(asil -enelitian
3
-atients
achiee
d
primary
endpoint
at 21
weeks
1&1 times more likely
to achiee end
point s insulin
group .p0?&???"/
1&1 times more likely
to achiee end
point s insulin
group .p0?&???"/
#ig$er baseline %1C redu&ed t$e &$an&e o' a&$ie(ing t$e "riar!
end"oint (P)0.05)
#lJ #onfidence 6nteral
-rimary
outcomes
P Value 4'.''')
)econdary outcomes
*R J =&?
*R J =&"
*R J 1&;
*R J 1&A
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.
(asil -enelitian
T5e #ro#ortion o6 #atients w5o ac5ie7ed 1)8 targets were
&9- ::
1)8
M !t 21 weeks
)econdary outcomes
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin
detemir, randomized, open-label, clinical trial of efficacy and safety in patients with type 2
diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care.
2013;36(5):1368-1376.
(asil -enelitian
Once-weekly
exenatide &n;)))-
Once- or twice daily
insulin detemir
&n;)'<-
D23 confidence interal
=
e
a
n

b
o
d
y

w
e
i
g
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t

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e

&
k
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-

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t

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>

w
k
s

.-2&@ to -2&?/
Body weight
)econdary outcomes
(asil -enelitian
*$ere +as a
"rogressi(e
de&rease in
bod! +eig$t
'ro baseline
at ea&$ (isit in
"atients
re&ei(ing
,-.; in
&ontrast/ bod!
+eig$t
in&reased in
deteir-treated
"atients grou"s
b! stud! end
Body weight
)econdary outcomes
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.
(asil -enelitian
)econdary outcomes
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.
(asil
-enelitian

T5e Psyc5ological .eneral Well-?eing

@uestionnairs

)howed improement from baseline to week 21 for

the 5+enatide group but not the detemir group, and

%here was no signicant difference between

treatment groups

T5e Im#act o6 Weig5t on Auality o6 /i6e-/ite

@uestionnaire

showed improements from baseline to week 21 for

bot5 grou#s compared with detemir with
significantly greater improement in the 5+enatide
group ersus the detemir group
-atient-reported *utcomes
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.
(asil
-enelitian
DA3 e+enatide- patients
and ;23 determir-treated
patients e+perienced at least
one treatment-emergent !5&
%he most common !5s in t
he 5IH group were
gastrointesti nal-related, with
spontaneously-reported nau-
sea occurring in ";3 of
patients ersus 23 in the
detemir group
7o patient died as a result
of an !5 in either group&
%here was no difference in
incidence of hypoglycemia
between groups &
)afety and %olerability
Kesimpulan

%reatment with 5+enatide resulted in a

signicantly greater proportion of patients
achieing target !"# than with insulin detemir,
with the added benet of weight loss not seen
with detemir&

5+enatide represents an alternatie treatment

option to insulin therapy in patients with type 2
diabetes using *!Ds with inadeGuate glycemic
control&
Daies ', (eller ), )reenan ), et al& *nce-weekly e+enatide ersus once- or twice-daily insulin detemir, randomized, open-label, clinical trial of efficacy
and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas& Diabetes Care. 2013;36(5):1368-1376.