2007 18 11-19

Thiazolidinedione 2

15 8.2 % 6.8 % 7.47 %

( sensitizer ) Thiazolidinedione ( mellitus ) ( Evidence-based medicine )

( glycohemoglobin, HbA1c ) 6.0 % 15 7.47 % 8.2 % 6.8 % 1

1997 2,3

100 7 12

3 STOP-NIDDM 4 Peroxisome proliferator-activated receptors ( PPARs ) 2

2

thiazolidinedione

( peroxisome proliferator-activated receptors, PPARs ) 5

5,6-8

9

5

thiazo- lidinedione ( thrifty gene ) Level A,B,C,E 1962 Neel 11 10

Level A ( Clear evi- ( triglyceride ) 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- 12 tive evidence from poorly controlled or uncontrolled studies ) PPAR- Level E ( Expert con- PPAR- sensus or clinical experience ) PPAR- Thiazolidinedione 2 13

PPAR- CYP2C8 CYP3A4 PPAR- Retinoid-X 16 24 5 ( retinoid-X receptor, RXR ) 60% PPAR- 5

PPAR- ( Glycohemoglogin A1c, HbA1c ) 1.0 1.6 % 5 5 Thiazolidinedione thiazolidinedione ( 1 ) 1997 ( Rezulin® ) 17-20 ( Level B ) ( 2 ) PPAR-

5,13,14 ( Level B )

21,22 ( Level rosiglitazone ( Avandia® ) B ) pioglitazone ( Actos® ) ( 3 ) PPAR- 15,16 ( Level A )

Thiazolidinedione ( ) 23-26 ( Level B )

PPAR- 5 thiazolinedione 15-23 Thiazolidinedione ( Level B ) thiazolinedione rosiglitazone 3 4 piogli- tazone 3 7 ( >99% ) 2 thiazolidinedione rosigli- 27 ( Level A tazone P450 CYP2C8 ( HbA1c ) 9% thiazolidinedione 100 150 pioglitazone P450 HbA1c HbA1c 14

9% 28-30 ( Level A ) ( vascular ( ) thiazolidinedione leak syndrome ) 42,43 ( Level E ) 2

metformin thiazo- 5’-AMP activated protein kinase lidinedione

31 ( Level B ) Thiazolidinedione 32-34 ( Level B ) thiazolidinedione rosiglitazone PPAR- 34 ( Level C ) 44 ( Level A ) PPAR- 42 ( Level E ) thiazolidinedione thia- 100 150 zolidinedione 36,37 ( Level C ) rosiglitazone HbA1c 45 ( Level C ) rosiglitazone thia- zolidinedione 46 ( Level B )

thiazolidinedione 47 ( Level B ) 38 ( Level E ) thiazolidinedione Thiazolidinedione 2 C- ( C-reactive protein, 2 48 ( Level CRP ) 39 ( Level C ) B ) Thiazolidinedione

40,41 ( Level C ) LDL-C Thiazolidinedione LDL-C thia- Thiazolidinedione zolidinedione LDL-C 49-51 ( Level B ) thiazolidinedione thiazolidinedione

52,53 ( Level B )

Thiazolidinedione ( adiponectin ) thiazolidinedione Thiazolidinedione 2 15

6~7%

42 ( Level E ) 54 ( Level B ) 2 thiazolidinedione

thiazolidinedione 2 2 23,24,27 ( Level A ) 40,55 ( 3 ) thiazo- ( level B ) lidinedione 60 ( Level C ) thiazo- lidinedione NYHA thiazolidinedione TRIPOD 13 ( Level B ) NYHA NY- HA Thiazolidinedione thiazolidinedione ( 1 ) troglitazone 61 ( Level C ) rosiglitazone pioglitazone

56 ( Level A ) thiazolidinedione metformin

2.5 ( triple therapy, sulfony- 3 56 ( Level A ) lurea/metformin/ thiazolidinedione ) thiazolidinedione 62 ( Level B )

54 ( Level B ) thiazolidinedione ( Non-alcoholic steatohepati- tis, NASH ) 58,59 ( Level C ) thiazolidinedione Thiazolidinedione troglitazone

( 2 ) thiazolidinedione 13 ( Level B ) 63 ( Level B ) 2~5% thiazolidinedione thiazolidinedione 15% 16

rosiglitazone QALYs ( quality-adjusted life-years ) 64 ( Level E ) 2

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Evidence for Thiazolidinedione, Insulin Sensitizers in the Treatment of Type 2 Diabetes Mellitus

Chih-Yuan Wang, and Tien-Chun Chang1

Department of Internal Medicine, Far-Eastern Memorial Hospital 1Department of Internal Medicine, National Taiwan University Hospital

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 . 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 )