100 7
Thiazolidinedione 2
15 8.2 %
6.8 % 7.47 %
( Insulin sensitizer ) Thiazolidinedione
( Diabetes mellitus )
( Evidence-based medicine )
1997
( glycohemoglobin, HbA1c ) 6.0 %
15 7.47
% 8.2 % 6.8 %1
2,3
3 STOP-NIDDM 4
thiazolidinedione
( peroxisome proliferator-activated receptors, PPARs )
5,6-8
9
t h i a z o - lidinedione
Level A,B,C,E
10
Level A ( Clear evi-
dence from well-conducted, generalizable, randomi- zed controlled trials that are adequately powered )
Level B ( Suppor-
tive evidence from well-conducted cohort studies )
Level C ( Suppor-
tive evidence from poorly controlled or uncontrolled studies )
Level E ( Expert con-
sensus or clinical experience )
Peroxisome proliferator-activated receptors ( PPARs )
2
2
5
5
( thrifty gene )
1962 Neel 11
( triglyceride )
12
PPAR- PPAR-
PPAR-
PPAR-
P P A R - R e t i n o i d - X ( retinoid-X receptor, RXR )
PPAR-
PPAR-
5
thiazolidinedione
1997 troglitazone ( Rezulin® )
5,13,14
( Level B )
rosiglitazone ( Avandia® ) pioglitazone ( Actos® )
PPAR- 15,16 ( Level A )
Thiazolidinedione
PPAR-
thiazolinedione
1 5 - 2 3
( Level B )
thiazolinedione rosiglitazone 3 4 piogli- tazone 3 7
( >99% ) 2
rosigli- tazone P450 CYP2C8
100 150 pioglitazone P450
CYP2C8 CYP3A4
16 24 5
Rosiglitazone 60%
pioglitazone
5
( Glycohemoglogin A1c, HbA1c ) 1.0 1.6 %5
Thiazolidinedione
( 1 )
17-20
( Level B )
( 2 ) PPAR-
21,22
( Level B )
( 3 )
( adiponectin )
23-26
( Level B )
5
Thiazolidinedione
thiazolidinedione
27( Level A
( HbA1c )
9% thiazolidinedione
HbA1c HbA1c
9% 28-30( Level A )
biguanide ( metformin ) thiazolidinedione
metformin 5’-AMP activated protein kinase
31( Level B )
32-34
( Level B ) sulfonylurea PPAR- 34 ( Level C ) PPAR-
thiazolidinedione
thia- zolidinedione
36,37
( Level C )
thia- zolidinedione
38( Level E )
thiazolidinedione
C- ( C-reactive protein, CRP )39( Level C )
40,41
( Level C )
Thiazolidinedione
Thiazolidinedione
thiazolidinedione
( vascular leak syndrome )42,43( Level E )
2
thiazo- lidinedione
Thiazolidinedione
thiazolidinedione rosiglitazone
44( Level A )
42( Level E )
100 150
rosiglitazone
HbA1c45 ( Level C ) rosiglitazone
46( Level B )
thiazolidinedione 47( Level B )
Thiazolidinedione
2
2 48( Level
B ) Thiazolidinedione
LDL-C
LDL-C thia-
zolidinedione LDL-C
49-51
( Level B )
thiazolidinedione
52,53
( Level B )
Thiazolidinedione ( adiponectin )
thiazolidinedione
54( Level B ) 2
thiazolidinedione 2
4 0 , 5 5
( level B )
t h i a z o - lidinedione
TRIPOD13( Level B )
Thiazolidinedione
( 1 ) troglitazone
rosiglitazone pioglitazone
56( Level A ) thiazolidinedione
2.5
3 56( Level A )
thiazolidinedione
54 ( Level B ) thiazolidinedione ( Non-alcoholic steatohepati- tis, NASH ) 58,59( Level C )
thiazolidinedione troglitazone
( 2 ) thiazolidinedione
2~5% thiazolidinedione
1 5 %
6~7%
42( Level E ) thiazolidinedione
2 23,24,27( Level A )
( 3 ) thiazo-
lidinedione 60( Level C )
N Y H A
thiazolidinedione N Y H A
N Y - HA
thiazolidinedione
61( Level C )
metformin
( triple therapy, sulfony- lurea/metformin/ thiazolidinedione )
62( Level B )
Thiazolidinedione
13( Level B )
63( Level B )
thiazolidinedione
r o s i g l i t a z o n e
QALYs ( quality-adjusted life-years ) 64 ( Level E )
2
HbA1
( QALYs )
r o s i g l i t a z o n e
64 2002 piogli-
t a z o n e
2.5 65( Level B )
2
thiazolidinedione
thiazolidinedione
thiazolidinedione
t h i a z o l i d i n e - d i o n e
thiazolidinedione
1.
2003
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Evidence for Thiazolidinedione, Insulin Sensitizers in the Treatment of Type 2 Diabetes Mellitus
Chih-Yuan Wang, and Tien-Chun Chang1
In Taiwan, the epidemiological research had showed increasing prevalence of hyperglycemia in general population, including adolescent. Previous studies showed that life style intervention could play a pivotal role to prevent ongoing diabetes mellitus in together with certain oral medication. Amongst, insulin sensitizers have dif- ferent pharmacological mechanism from conventional oral hypoglycemic agents. Insulin sensitizers can not on- ly improve blood glucose control, but decrease insulin resistance via activation peroxisome proliferator-activated receptors, PPARs. This review will focus on recent evidence-based data for insulin sensitizers to elucidate se- veral important issues, including their side effects, pharmacological mechanism, pharmacokinetics, and phar- macoeconomics. ( J Intern Med Taiwan 2007; 18: 11-19 )
Department of Internal Medicine, Far-Eastern Memorial Hospital
1Department of Internal Medicine, National Taiwan University Hospital
