BUC TIP CAN MI TRONG

IU TRI I THO UNG TP 2

VAI TR CA THUC C CH MEN
DPP- 4
TRN-QUANG-KHNH
BO MN NO TT
HYD PHCM
T2DM represents ~90%95% of cases (Centers for Disease Control and Prevention. National Diabetes Fact Sheet, 2005. Atlanta, Ga: US Department
of Health and Human Services; 2005.)
Adapted from nternational Diabetes Federation. Diabetes Atlas. 2nd ed. 2003; 3rd ed. 2006.
T nh hung dn 246 triu T nh hung dn 246 triu
ngui trn ton th gii ngui trn ton th gii
M chu
2007: 45 miIIion
u chu
2007: 53 miIIion
Phi chu, ia trung hi
v Trung ng
2007: 35 miIIion
NA v Ty TBD
2007: 114 miIIion
T2DM represents ~90%95% of cases (Centers for Disease Control
and Prevention. National Diabetes Fact Sheet, 2005.
Atlanta, Ga: US Department of Health and Human Services; 2005.)
Adapted from nternational Diabetes Federation. Diabetes Atlas. 2nd ed. 2003; 3rd ed. 2006.
T I T chu v Ty TBD, 2007
>20% 14%-20% 10%-14% 8%-10%
6%-8% 4%-6% <4%
T I bnh di tho dung*: chu T I bnh di tho dung*: chu
2.9 (2.0%) ndonesia
1.5 (9.9%) Malaysia
39.8 (4.3%) China
3.2 (7.2%) Thailand
0.9 (6.4%) Australia
3.9 (7.6%) Korea
0.4 (11.9%) Singapore
40.9 (6.2%) ndia
Dn s T (triu) t 20-
79 tui (% dn s chung)
Quc gia
0.8 (5.7%) Taiwan
0.2 (7.7%)
New
Zealand
7.0 (7.2%) Japan
3.2 (4.0%) Vietnam
23.0 M
36.2 M
|57.0%
14.2 M
26.2 M
|85%
48.4 M
58.6 M
|21%
43.0 M
75.8 M
|79%
7.1M
15.0 M
|111%
39.3 M
81.6 M
|108%
M = million, AFR = Africa, NA = North America, EUR = Europe,
SACA = South and Central America, EMME = Eastern Mediterranean and Middle East,
SEA = South-East Asia, WP = Western Pacific
Diabetes Atlas Committee. Diabetes Atlas 2
nd
Edition: DF 2003.
Dich t hoc T: 2003-2025
WorId
2003 = 194 M
2025 = 333 M
| 72%
AFR
NA
SACA
EUR
SEA
WP
19.2 M
39.4 M
105%
EMME
2003
2025
Bnh I vng mac:
nguyn nhn chnh gy
m la
Leading cause
of blindness
in adults
1,2
Bnh I thn:
nguyn nhn
chnh suy thn giai
doan cui
Bin chng tim
mach: 80% bn
T t vong do
bin c TM
t quy:
tng 2-4 ln nguy co
t vong do tim mach
v dt quy
Bnh I thn kinh:
nguyn nhn chnh
gy doan chi khng
do chn thuong
Cc bin chng man tnh ca T tp 2
Bin chng
mach mu nh
Nhi mu co tim
cp
HbA
1c
37%
14%
iu tri tch cuc Im gim nguy co
bin chng man T
T vong Iin
quan T
21%
1%
Stratton M, et al. BMJ 2000; 321:405412.
Stratton M, et al. BMJ 2000; 321:405412
7
Adapted from Buse JB et al. n illiams Textbook of Endocrinology. 10th ed. Philadelphia, Saunders, 2003:14271483; Buchanan TA Clin
Ther 2003;25(suppl B):B32B46; Powers AC. n: Harrison's Principles of Internal Medicine. 16th ed. New York: McGraw-Hill, 2005:21522180;
Rhodes CJ Science 2005;307:380384.
Co ch bnh sinh T tp 2 Co ch bnh sinh T tp 2
TNG UNG HUYT
Gan
nsulin deficiency
TNG SN XUT GLUCOSE
KHNG INSULIN
Tuy
Co v m
Tng tit glucagon
slet
Giam tit insulin
Gim tit
insulin
T bo
alpha
T bo
beta
Vi tr tc dung cc nhm thuc T
Kahn CR, Saltiel AR. n: Kahn CR et al, eds.
Joslin's Diabetes Mellitus. 14th ed. Lippincott Williams & Wilkins; 2005:145168;
Del Prato S, Marchetti P. Horm Metab Res. 2004;36:775781; Porte D Jr, Kahn SE. Clin Invest Med. 1995;18:247254.
Sn xut
gIucose tai
gan
khng
insuIin
GIucagon
(t bo )
InsuIin
(t bo )
Gan
Suy gim chc nng t bo
Co Co
M m M m
Tuy
Dung nap
GIucose
SU,GIinide
MET
TZD
AGI
INSULIN
Luu d dng thun ADA/EASD
2009 -2011
Chn don
Li sng
+
Metformin
Li sng+Metformin
+
PiogIitazone
(Khng h H, ph
suy tim, mt xong)
Li sng+Metformin
+
SuIfonyIurea
Li sng+Metformin
+
InsuIin tch cuc
Li sng+Metformin
+
InsuIin nn
Li sng+Metformin
+
GLP1
(Khng h H, gim cn,
Bun nn/nn)
Li sng+Metformin
+
PiogIitazone
+
SuIfonyIurea
Li sng+Metformin
+
BasaI InsuIin
Tier 2: iu tri cn thm dinh thm
Tier 1: iu tri nn tng duoc thm dinh tt
Buc Buc 1 1
Buc 2 Buc 2 Buc 3 Buc 3
ng vn amyIin, GIinides,
c ch men DPP-4 c th
duoc s dung trn tng
di tuong ph hop
*Khi cn nhc trnh
tnh trang ha H
25
21
45
7
37
10
46
8
0 10 20 30 40 50
KS H tt
HbA1c < 7.0%
KS H khng
tt HbA1c >
9.5%
2003
2002
2000
1997
Diabetes Physician Recognition Program, average performance of applicants, 1997-2003 data.
% bnh nhn
Mc d kim sot bnh T tp Mc d kim sot bnh T tp 2 2
Bnh i tho dung tp 2 Bnh i tho dung tp 2
1. Dich t hoc ca bnh T tp 2:
NG LO NGAI NG LO NGAI
2. Cc bin chng man tnh ca bnh T tp 2:
NANG N, TNG TY LE T VONG NANG N, TNG TY LE T VONG
3. Hiu qu ca vic diu tri tch cuc:
LM GIM TN SUT BIN CHNG MAN LM GIM TN SUT BIN CHNG MAN
4. Mc d kim sot T tp 2:
CHUA AT YU CU CHUA AT YU CU
5. Nhu cu c thm thuc mi:
C NHU CU C NHU CU
Amlel S ulabeL Med 20082324334 uavls 1ML eL al ! Clln Lndocrlnol MeLab 20109322407
Ha dung huyt Ha dung huyt
L ro cn chnh trong vic kim sot
tch cc trn bnh nhn di tho dng
tp 2
Cc con ha dung huyt khng triu chng
c th khng duoc ghi nhn
W Trong mt NC don h
trn BN T, hon 50%
trung hop ha dung
huyt khng triu
chng duoc pht hin
qua theo di Iin tuc
dung huyt
1
W Cc nh nghin cu
khc cng bo co pht
hin tuong tu
2,3
1. Copyright 2003 American Diabetes Association. Chico A et al. Diabetes Care. 2003;26(4):11531157.
Reprinted with permission from the American Diabetes Association.
2. Weber KK et al. Exp Clin Endocrinol Diabetes. 2007;115(8):491494.
3. Zick R et al. Diab Technol Ther. 2007;9(6):483492.
BN vi 21 tai bin ha dung
huyt khng nhn bit , %
0
25
50
75
100
Tt c
BN T
T
Type 1

n
h

n
h

n
,

7
T
Type 2
55.7
2.5
4.
n=70 n= n=40 40 n=30 n=30
Yu t nguy co ha dung huyt
W Dng SuIfonyIurea/InsuIin
W Ngui In tui
W Mc bnh d Iu
W Ch d n khng tun th
W Tp th Iuc qu sc
W C gng dat muc tiu A1c qu thp
W Nhin di
W C tin cn ha dung huyt khng nhn bit
W Nghin ruou
25
0
5
10
15
20
ACCORD ADVANCE
Tch cuc
Thung quy
%

b

n
h

n
h

n

c

t

n
h

t

m

t

c
o
n

h
a

d
u

n
g

h
u
y

t
VADT
Ha dung huyt thung xy ra trong
nhm diu tri tch cuc
ACCORD mc d cn tro gip trong con
ha dung huyt
ACCORD study. N Engl J Med 2008;358(24): 2545-2559.
16.2
5.1
10.5
3.5
0
3
6
9
12
15
18
B

n
h

n
h

n

(
%
)
Cn bt ky tro gip
Cn tro gip y khoa
iu tri tch cuc
(muc tiu HbA
1c
<6%)
iu tri thung quy
(muc tiu HbA
1c
7.0 to 7.9%)
ACCORD: t sut cao trong nhm
bnh nhn ha dung huyt nng
Nguyn nhn tng t sut cn duoc kim chng thm; tuy
nhin ha dung huyt nng lun lun duoc nhn manh
3.3%
1.2%
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Khng c con ha H nng C con ha H nng
T

s
u

t

c
h
u
n
g

(
%
)
ACCORD study. N Engl J Med 2008;358(24): 2545-2559.
Cc nhm thuc diu tri T dang
ung v nguy co ha dung huyt
CC THUC TM N NGUY CO CAO HA UNG HUYT
W Cc thuc kch thch t bo tuy tit insuIin
Sulfonylureas
Glinide (rapaglinide/nateglinide)
CC THUC T NGUY CO HA UNG HUYT
W Ci thin d khng insuIin
Biguanide-metformin
Thiazolidinediones (pioglitazone/rosiglitazone)
W Cc thuc Incretin
c ch DPP-IV (sitagliptin, vildagliptin, saxagliptin, alogliptin)
W Gim hp thu gIucose
c ch men alpha-glucosidase (acarbose, voglibose)
colesevelam)
Lich s pht hin hormone incretin Lich s pht hin hormone incretin
1302
Quan st du tin ghi nhn mt cht sn xut tai rut
c th kch thch tuy ni tit (Bayliss & Starling)
S dung ln du tin thut ng "in(testine)-(se)cretion-
in(sulin) (La Barre)
1332
Hiu ng incretin duoc chng minh (Mc ntyre & Elrick)
1364
GIP l hormone incretin du tin duoc tm thy ngui
1373
Chng minh "hiu ng incretin suy gim trn bnh
nhn T tp 2 (Nauck)
1386
GLP-1 l hormone incretin th nh duoc tm thy ngui
1387
Tm ra cht ging ha incretin (DPP-4) 133S
Cc hormone incretin Cc hormone incretin
Y
A
E
G
T
F
I
S
D
Y
S
I
A
M
D
K
I
H
Q
Q
D
F
V
N
W
L
L
A
Q
K
G
K
K
N
D
W
K
H
N Q
T
I
GIP: GIucose-dependent InsuIinotropic Peptide
H
A
E
G
T
F
T
S
D
V
S
S
Y
L
E
G
Q
A
A
K
E
F
I
A
W
L
V
K
G
R
G
GLP-1: GIucagon-Iike Peptide-1
Amino acids shown in orange are homologous with the structure of glucagon.
Cc hormone incretin diu ha nng d
insuIin v gIucagon
GLP-1 = glucagon-like peptide-1; GP = glucose insulinotropic polypeptide
from Kieffer T. Endocrine Reviews. 1999;20:876913. Drucker DJ. Diabetes Care. 2003;26:29292940. Nauck
MA et al. Diabetologia. 1993;36:741744.
Tuy Rut
Tn hiu dung cht
GIucose
Tn hiu hormone
W GLP-1
W GIP
|GIucagon
(GLP-1)
| InsuIin
(GLP-1,GP)
Tn hiu TK
T bo -
T bo .
Ha H
Tng hop GLP-1 v GIP
T bo L
(hi trng)
ProgIucagon
GLP-1 [7-37]
GLP-1 [7-36NH
2
]
T bo K
(t trng)
ProGIP
GIP [1-42]
Ging ha GLP-1 v GIP
Mao mach
Mao mach
T bo K
T bo L
GIP [3-42]
BT HOT
DPP-4
GIP [1-42]
HOT TINH
GLP-1[7-36NH
2
]
HOT TINH
GLP-1 [9-36NH
2
]
BT HOT
DPP-4
ProgIucagon
GLP-1 [7-37]
GLP-1 [7-36NH
2
]
ProGIP
GIP [1-42]
DipeptidyI peptidase-4 (DPP-4)
WThuc nhm enzyme protease
WBt hoat > 50% GLP-1 trong ~ 1 min
> 50% GIP trong ~ 7 min
Adapted from Nauck MA, et al. J Clin Endocrinol Metab. 1986; 63: 492498.
Nghim php dung nap gIucose so vi GIucose truyn TM
G
I
u
c
o
s
e

(
m
g
/
d
L
)
0
50
100
150
200
-30 0 30 60 90 120 150 180 210
Thi gian (pht)
I
n
s
u
I
i
n

(
p
m
o
I
/
L
)
0
100
200
300
400
-30 0 30 60 90 120 150 180 210
Thi gian (pht)
Hiu ng incretin Hiu ng incretin
Ung TM
50 g GIucose
N=6
GLP GLP- -1: tc dng trn ngui 1: tc dng trn ngui
GLP-1 duoc tit ra t
t bo L t trng
v hi trng
GLP-1 c tc dung.
W Kch thch tit insuIin
phu thuc gIucose
W c ch tit gIucagon
W Chm Im trng da dy
dng vt thuc nghim:
W Tng khi Iuong v ci thin
chc nng t bo
W Ci thin su nhy cm
vi insuIin
W Gim cm gic thm n
Sau khi n.
Drucker. Curr Pharm Des. 2001
Drucker. Mol Endocrinol. 2003
Nslund E, et al. Am J Physiol. 1999;277:R910-R916.
GLP GLP- -1 ko di thi gian Im trng 1 ko di thi gian Im trng
da dy da dy
0
10
20
30
40
50
60
70
80
90
100
0 20 40 60 80 100 120 140 160 180
Time (min)
G
a
s
t
r
i
c

E
m
p
t
y
i
n
g

(
%

r
e
m
a
i
n
i
n
g

i
n

s
t
o
m
a
c
h
)
GLP-1
SaIine
p ng tit InsuIin v GIucagon sau n p ng tit InsuIin v GIucagon sau n
trn bn T tp 2 trn bn T tp 2
Adapted from Mller WA et al N Engl J Med 1970;283:109115.
T tp 2 (n=12)
Nhm chng (n=11)
Thi gian (pht)
G
l
u
c
a
g
o
n
(

g
/
m
l
)
140
90
60
100
110
120
130
Glucagon khng c ch duoc
0 60 120 180 240

n
s
u
l
i
n
(

U
/
m
l
)
150
0
30
60
90
120
Mt dinh tit insulin sm
360
G
l
u
c
o
s
e
(
m
g
/
1
0
0

m
l
)
80
240
110
270
300
330
Ba n
GT=impaired glucose tolerance; NGT=normal glucose tolerance
Adapted from Mitrakou A, et al. N Engl J Med. 1992; 326: 2229.
GIucagon
25
30
35
40
45
p
m
o
I
/
L
Time (min)
-60 0 60 120 180 240 300
NGT
IGT
0
InsuIin
200
400
600
p
m
o
I
/
L
GIucose
GIucose
50
100
150
200
250
m
g
/
d
L
NGT
IGT
NGT
IGT
p ng tit InsuIin v GIucagon sau n p ng tit InsuIin v GIucagon sau n
trn bn tin T trn bn tin T
Hiu ng Incretin suy gim trn Hiu ng Incretin suy gim trn
bnh nhn T tp 2 bnh nhn T tp 2
pA0.05
R=immunoreactive
Adapted from Nauck M et al Diabetologia 1986;29:4652.
Gim hiu ng
incretin
Hiu ng incretin
bnh thung
Glucose dung ung (50 g/400 ml) Glucose truyn TM
0
10
10
15
20
g
l
u
c
o
s
e

m

u

T
M


(
m
m
o
l
/
L
)
5
60 120 180
Thi gian (pht)
0
40
60
80

R

i
n
s
u
l
i
n

(
m
U
/
L
)
20
Nhm chng (n=8) T tp 2 (n=14)
0
10
15
20
5
Thi gian (pht)
0
40
60
80

R

i
n
s
u
l
i
n

(
m
U
/
L
)
20
5 10 60 120 180 5
10 60 120 180 5 10 60 120 180 5

g
l
u
c
o
s
e
m

u

T
M

(
m
m
o
l
/
L
)
Nng d GLP Nng d GLP- -1 gim trn di tuong 1 gim trn di tuong
tin T v T tin T v T
Toft-Nielsen et al. J Clin Endocrinol Metab. 2001
20
15
10
5
0
0 60 120 180 240
Thi gian (pht)
G
L
P
-
1

(
p
m
o
I
/
I
)
*
*
*
*
*
*
*
*
n sng
BT
T tp 2
RLDN
gIucose
*P<0.05 T tp 2 so vi chng bnh thung
Hoat tnh GLP Hoat tnh GLP- -1 khng bi nh hung 1 khng bi nh hung
trn bn T tp 2 trn bn T tp 2
Chng bt (n=9)
T tp 2 (n=9)
Tc d thp= 0.4 pmol kg
1
min
1
Tc d cao=1.2 pmol kg
1
min
1
so vi nhm chng bnh thung
Adapted from Nauck MA et al J Clin Invest 1993;91:301307.
GLP-1 truyn tc d thp
GLP-1 truyn tc d cao
0
10
20
30
40
50
60
7.4
51.4
7.5
38.2
P=NS
P=NS
GLP GLP- -1 Im gim nng d gIucagon v 1 Im gim nng d gIucagon v
H trn bn T tp 1 H trn bn T tp 1
Creutzfeldt WO, et al. Diabetes Care. 1996;19:580-6.
0
2
4
6
8
10
12
-30 0 30 60 90 120 150 180 210 240
Time (min)
G
I
u
c
a
g
o
n

(
p
m
o
I
/
L
)
0
50
100
150
200
250
300
350
-30 0 30 60 90 120 150 180 210 240
Time (min)
P
I
a
s
m
a

G
I
u
c
o
s
e

(
m
g
/
d
L
)
*
* *
*
*
*
*
*
GLP-1
P < .001
PIacebo
GLP-1 so vi PIacebo
PIacebo
GLP-1
P < .001
*
*
*
*
*
* *
GLP-1 so vi PIacebo
GLP GLP- -1 truyn TM Iin tuc gip n dinh 1 truyn TM Iin tuc gip n dinh
H trong ngy H trong ngy
Rachman et al. Diabetologia. 1997
T tp 2
T tp 2 +
GLP-1
Chng
0
0600 1000 1400 1600
G
I
u
c
o
s
e

(
m
m
o
I
/
I
)
16
Thi gian
fn sng fn trua Ba l
12
8
4
0200 2200
(1.2 pmol/kg/min)
*P<0.05
0.0
0.5
1.0
1.5
2.0
2.5
3.0
*
*
*
*
*
*
*
*
0
5
7.5
10
12.5
15
GLP-1
SaIine
*
*
*
*
*
*
*
Hiu qu ca GLP Hiu qu ca GLP- -1 trn bn T tp 2 1 trn bn T tp 2
-30 0 60 120 180 240
Thi gian (pht)
-30 0 60 120 180 240
Thi gian (pht)
Truyn GLP-1 Truyn GLP-1 Truyn GLP-1 Truyn GLP-1
Glucose (mmol/l) C-peptide (nmol/l)
-30 0 60 120 180 240
Thi gian (pht)
0
5
10
15
20
25
30
*
*
*
*
Truyn GLP-1 Truyn GLP-1
Glucagon (pmol/l)
Nauck et al. Diabetologia. 1993
2.5
17.5
Ngy 1
Ngy 3
Ngy 5
Chng + GLP-1
Farilla et al. Endocrinology. 2003
GLP GLP- -1 bo tn hnh th v chc nng 1 bo tn hnh th v chc nng
tiu do Langerhans tiu do Langerhans in vitro in vitro
Khi luong
t bo 8
Tng sinh
t bo 8
T bo 8 cht theo
chuong trnh
Farilla et al. Endocrinology. 2002
0
4
8
12
16
Chng GLP-1
0
0.5
1.0
1.5
2.0
2.5
Chng
0
10
20
30
ChngI
P<0.001
P<0.05
P<0.01
Hiu qu ca GLP Hiu qu ca GLP- -1 1 In t bo In t bo
chut Zucker (T bo ph) chut Zucker (T bo ph)
GLP-1 GLP-1
(mg)
(%)
(%)
Cc ng dung hiu ng incretin trong Cc ng dung hiu ng incretin trong
diu tri T tp 2 diu tri T tp 2
1. Cc cht tuong tu GLP-1 v GIP nhung d
khng vi enzyme DPP-4:
- Cht dng vn GLP-1, GLP-1 gn kt vi
Protein
- Peptide thin nhin d khng vi DPP-4
2. Cc hoat cht ko di thi gian bn hy ca
hormone incretin ni sinh:
- Cht c ch DPP-4
ng vn GLP ng vn GLP- -1: (Exendin 1: (Exendin- -4) 4)
- Protein t nuc bot ca Gila monster
- Tc dung tuong tu GLP-1 vi T1/2 di
- Nng d dinh v T1/2 ~ 2 gi
- Cu trc tuong duong GLP-1 ( > 50%)
- khng vi DPP-4
- Gn kt vo thu th GLP-1 trn t bo 8 in vivo
GLP-1 H A E G T F T S D V S S Y L E G Q A A K E F A W L V K G R NH2
Exenatide H G E G T F T S D L S K Q M E E E A V R L F E W L K N G G P S S G A P P P S - NH2
Vi tr tc dung ca DPP-4
c ch DPP c ch DPP- -4 Im tng tc dung GLP 4 Im tng tc dung GLP- -1 1
GLP-1
bt hoat
(>80%)
GLP-1
hoat tnh
Ba n
DPP-4
Rut tit
GLP-1
GLP-1 t

=1-2 pht
DPP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1
Rothenberg P, et al. Diabetes. 2000; 49(suppl 1): A39. Abstract 160-OR.
Deacon CF, et al. Diabetes. 1995; 44: 1126-1131.
DPP-4=dipeptidyl peptidase-4; T2DM=type 2 diabetes mellitus
Adapted from Unger RH. Metabolism. 1974; 23: 581593. Ahrn B. Curr Enzyme Inhib. 2005; 1: 6573.
InsuIin
G GIucagon
Ci thin KS
dung huyt
Hiu ng
Incretin
ko di
Ci thin chc
nng tiu do tuy
c ch DPP-4
G InsuIin
GIucagon
TNG UNG HUYT
Gim dp
ng
Incretin
RL chuc nng
tiu do tuy
T T2
c ch DPP c ch DPP- -4 ci thin hiu ng 4 ci thin hiu ng
Incretin trn bn T tp 2 Incretin trn bn T tp 2
Khc bit H trung bnh 24
gi : - 32.8 mg/dL (- 1.82
mmol/L) p<0.001
Adapted from Brazg RL et al. Poster presented: at American Diabetes Association; June 1014, 2005; San Diego, Calif.
SitagIiptin thm vo Metformin ci thin SitagIiptin thm vo Metformin ci thin
dung huyt dung huyt 24 24h bnh nhn di tho h bnh nhn di tho
dung tp dung tp 2 2
G
l
u
c
o
s
e

(
m
g
/
d
L
)
8:00
Ngy 1
13:00 19:00 0:00
Ngy 2
7:30
100
120
140
160
180
240
200
220
Liu 1
7:30
Liu 2
18:30
Sng Trua Ti
Placebo + metformin (n=13)
Sitagliptin 50 mg b.i.d. + metformin (n=15)
Thi gian
SitagIiptin mt In mi ngy cho thy SitagIiptin mt In mi ngy cho thy
hiu qu gim dung huyt tuong tu hiu qu gim dung huyt tuong tu
nhu gIipizide khi thm vo metformin nhu gIipizide khi thm vo metformin
SitagIiptin 100 mg qd + Metformin
(n=382)
GIipizide + Metformin (n=411)
T
h
a
y

d

i

H
b
A
1
c

t
r
u
n
g

b

n
h
Thay di trung bnh so vi ban du (cho c 2 nhm): - 0.67%
6.0
6.2
6.4
6.6
6.8
7.0
7.2
7.4
7.6
7.8
8.0
8.2
8.4
0 12 24 38 52
Thi gian (tun)
phn tch per-protocol; -0.51% v -0.56% cho sitagliptin v glipizide trong phn tch LOCF
Nauck et al, Diabetes Obesity Metabolism 9: 194 205, 2007
SitagIiptin mt In mi ngy c d an ton v SitagIiptin mt In mi ngy c d an ton v
dung nap tt hon so vi GIipizide dung nap tt hon so vi GIipizide
GIipizide (n=584)
SitagIiptin 100 mg (n=588)
p<0.001
Thay di cn nng
86
88
90
92
94
0 12 24 38 52
Thi gian (tun)
B
o
d
y

w
e
i
g
h
t

(
k
g
)
SitagIiptin 100 mg qd (n=382)
GIipizide (n=411)
Nauck et al, Diabetes Obesity Metabolism 9: 194 205, 2007
between groups = 2.5 kg (p<0.001)
Tai bin ha dung huyt
32%
4.9%
0
10
20
30
40
50
Tun 52
I
n
c
i
d
e
n
c
e

(
%
)
N=492 bin c N=37 bin c
SitagIiptin kim sot dung huyt khng km SitagIiptin kim sot dung huyt khng km
hon GIimepiride, vi ti I mi mc ha dung hon GIimepiride, vi ti I mi mc ha dung
huyt thp hon v gim cn nhiu hon huyt thp hon v gim cn nhiu hon
Ha dung huyt sau 30 tun
Thay di cn nng tun 30
LS=least-squares.
Dia Obes&Meta 13: 160-168,2011
7
22
0
5
10
15
20
25
B
N

c

2
1

c
o
n

h
a
d
u

n
g

h
u
y

t
,

%
SitagIiptin 100 mg GIimepiride 1-6 mg
-0.8
1.2
-1.0
-0.5
0.0
0.5
1.0
1.5
T
h
a
y

d

i

c

n

n

n
g

t
r
u
n
g

b

n
h

s
o

v

i

b
a
n

d

u
,

k
g
n=516 n=518
n=465
n=461
Tt c bnh nhn khng kim sot tt vi metformin don tri Iiu
Thay di HbA
1c
so vi ban du tun 30
(Kt cuc chnh)
-0.47
-0.54
-0.8
-0.6
-0.4
-0.2
0.0
T
h
a
y

d

i

t
r
u
n
g

b

n
h


(
9
5
%

K
T
C
)
H
b
A
1
c
s
o

v

i

b
a
n

d

u
,

%
n=443 n=436
Mc khng km
hon dinh truc =
0.40%
(95%CI)
0.07% (-0.03, 0.16)
ln tr Kt hop 2 nhm thuc
MET +
GLP-1 hay DPP4
TZD
GIinide hay SU
TZD + GLP-1 hay DPP4
MET +
CoIeseveIam
AGI
MET DPP4 GLP1 TZD
AGI
MET +
GLP1 hay
DPP4
+
TZD
GIinides hay SU
nsulin + cc thuc khc
MET +
GLP1 hay DPP4 hay
TZD
SU hay
GIinides
MET +
GLP1 hay
DPP4
+TZD
GLP1 hay
DPP4
+SU
TZD
NET +
CLP1
hay
DPP4 +SU
TZD
CLP1
hay
DPP4
+TZD
Kt hop 3 nhm thuc
Khng triu chng,
chua dng thuc
C triu chng
tng dung huyt
LI SNG TCH CUC
A1C 6.5-7.5%
A1C 7.6-9.0% A1C >9%
Kt hop 2 nhm thuc
Kt hop 3 nhm thuc
Kt hop 3 nhm thuc
Khuyn co AACE Khuyn co AACE
ADA/ EASD ADA/ EASD
W W Y hoc chng c Y hoc chng c
W W Khuyn co dng Khuyn co dng
insuIin sm insuIin sm
W W Ch dn hiu qu v Ch dn hiu qu v
gi thnh truc tip ca gi thnh truc tip ca
thuc thuc
W W Kt hop hai nhm Kt hop hai nhm
thuc, han ch kt hop thuc, han ch kt hop
nhiu nhm thuc nhiu nhm thuc
AACE/ ACE AACE/ ACE
W W Cho php s dung moi Cho php s dung moi
nhm thuc duoc FDA nhm thuc duoc FDA
chp thun chp thun
W W Nhn manh nguy co ha Nhn manh nguy co ha
dung huyt nng dung huyt nng
W W Cho nhiu chon Iua v Cho nhiu chon Iua v
kt hop diu tri ph hop kt hop diu tri ph hop
vi tng c nhn ngui vi tng c nhn ngui
bnh bnh
So snh ADA V AACE So snh ADA V AACE
Kt Iun Kt Iun
1. Hormone incretin (GLP-1 v GP) c tc dung
lm tng tit insulin v gim tit glucagon ca
tiu do tuy
2. Tip cn bnh nhn di tho dung tp 2 dua
trn cc thuc incretin gp phn ci thin kim
sot dung huyt v gim thiu nguy co ha
dung huyt
3. Sitagliptine l cht c ch men DPP-4 c hoat
tnh ko di dng mt ln duy nht gip ci thin
kim sot dung huyt hiu qu trn bnh nhn
di tho dung tp 2
XIN CM ON QU XIN CM ON QU
NG NGHIEP NG NGHIEP