Effects of Pioglitazone and Rosiglitazone on Glucose and the Cardiovascular Risk Factors in Patients with Type 2 Diabetes: A Meta-analysis

(1)

Pioglitazone과 Rosiglitazone이 제2형 당뇨환자의 혈당조절 및 심혈관계 위험인자에 미치는 효과에 대한 메타분석

이재경·이의경*^,#

주식회사 유한양행 개발실, *숙명여자대학교 임상약학대학원

(Received August 15, 2009; Revised November 3, 2009; Accepted November 4, 2009)

Effects of Pioglitazone and Rosiglitazone on Glucose and the Cardiovascular Risk Factors in Patients with Type 2 Diabetes: A Meta-analysis

Jae Kyoung Lee and Eui Kyung Lee*^,#

Pharmaceuticals Development Team, Yuhan corporation, Seoul 156-754, Korea

*Graduate School of Clinical Pharmacy, Sookmyung Women's University, Seoul 140-702, Korea

Abstract

— A meta-analysis of 63 randomized controlled trials of Pioglitazone and Rosiglitazone in patients with type 2 dia- betes was conducted. Pioglitazone significantly lowered fasting plasma glucose and triglyceride (TG) level and increased high-density lipoprotein cholesterol (HDL) level. Rosiglitazone significantly lowered hemoglobin A1C level and fasting plasma glucose, whereas it increased all kinds of lipids (HDL, LDL (low-density lipoprotein cholesterol), TG, total cho- lesterol). In comparison, glucose lowering effect was higher in Rosiglitazone, and Pioglitazone produced a more favorable lipid profile.

Keywords □

Pioglitazone, Rosiglitazone, type 2 diabetes, meta-analysis

1970

^년대

30

^만명을^넘지^않던^국내^당뇨병^환자^수가

1998

^년

300

만명에서현재는전체인구의

10%

인

400

만명에이른다

.

¹⁾뿐 만아니라

,

당뇨병으로인한사망률또한증가추세로지난

10

년간

11.6%

^가^증가하여^{우리나라의}

4

^대^{사망원인이}^되었고

,

^한

국인의당뇨병사망률이경제협력개발기구

(OECD)

가입국중가 장높은것으로나타나²⁾보다적극적인당뇨병관리의필요성이 대두되었다

.

현재국내·외에서사용되는경구혈당강하제를살펴보면설

폰요소

(sulfonylurea)

^계^약물이^가장 ^많으며 ^{바이구아나이드}

(biguanide)

^계의

metformin

^과^소장에서^포도당^흡수를^지연시키

는 알파

-

글루코시다제 억제제

(alpha-glucosidase inhibitor)

인

acarbose,

^그리고^인슐린^저항성을^{개선시키는}

thiazolidinedione

계약물등이있다

.

³⁾

이중본연구의대상약물은

thiazolidinedione(

이하

TZD),

또 는

glitazone

^계^{경구혈당강하제인}

Pioglitazone

^과

Rosiglitazone

이다

. TZD

^는^{지방세포와}^{혈관세포에}^주로^존재하는

peroxisome

proliferator activated receptor gamma(PPAR

γ

)

를활성화시켜인 슐린저항성을감소시킨다

.

또한

TZD

는혈당을낮추는것외에 도혈중지질구성

(lipid profile)

^을^{개선시키는}^등^심혈관계^위험인

자에대체적으로긍정적으로작용한다고알려져있어

,

당뇨환자 의심혈관계합병증을예방하는효과가있다고보여진다

.

Pioglitazone

^과

Rosiglitazone

^은^{세계적으로}^다양한^함량의^제

품이 시판되고 있고

,

그사용이증가되고 있다

.

국내에서도

Rosiglitazone

^제제가^시판되고^있으며

, Pioglitazone

^은^국내에^오

리지날 이외에다수의 제네릭 제제도 시판되고있다

.

^특히

Rosiglitazone

제품은

2000

년한국에처음런칭되자마자판매

1

위

에오를정도로위세를떨쳤으나

, 2007

^년에^심혈관계^부작용^및

골절에대한위험이이슈화되고이후부작용논란이계속되면서

, Pioglitazone

오리지날및그제네릭제제들이

Rosiglitazone

의 점유율을잠식하며성장해나가고있다

.

한편

,

^이러한

TZD

^약물의^{임상시험은}^매우^부족한^실정이고

,

특히국내의기존연구는몇몇기관에서의임상시험을통한연

구들에국한되어있기때문에두

TZD

^제제의^효과를^종합적으

로비교하기에는다소부족한측면이있다

.

#본논문에관한문의는저자에게로

(

^전화

) 02-710-9799 (

^팩스

) 02-6395-1214

(E-mail) [email protected]

(2)

따라서본연구의목적은현재까지국내·외에서시행되었던 임상시험에관한연구문헌들을대상으로한메타분석을시행하여

Pioglitazone

과

Rosiglitazone

이혈당및기타심혈관계위험인자

,

즉

,

^총 ^{콜레스테롤}

(TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol(HDL),

중성지방

(triglyceride,

이하

TG),

혈압

(BP),

체중등

)

에미치는효과를저 용량및고용량투여군에서각각비교해봄으로써기존연구들 의결과들을종합적으로파악하고자함이며

,

이를통해임상에 서의효율적인약제선택에기여하고자한다

.

연구 방법

임상시험논문의수집을위해상향식접근법을이용한온라인

검색을시행했다

. 1

차적으로검색은

Pubmed

를사용하였으며

,

국

내논문검색을위해서는

Koreamed, KRIST

등을비롯하여국회 도서관소장자료검색프로그램등을이용하였다

. 2008

^년

2

^월까

지발표된

TZD

^약물의

randomized controlled trial(RCT)

^를^모

두수집한후

,

^초록검토^과정을^거쳐^{후보논문을}^{선정하였다}

.

본연구의대상논문선정

/

제외기준및질평가기준에준하여 전문검토를통해최종논문을선정하였다

.

^선정

/

^제외^기준과^관

련하여메타분석을위한본연구에서의대상논문은

RCT

이어야 하며

,

총

25

명이상의성인환자를대상으로하고

,

대상약제의 투여군은최소

10

^명^이상인^것으로^하였다

.

^{치료약물의}^투여에

있어서는

, TZD

약물이장기적으로치료해야효과가있음이알

려져있고

,

특히당화혈색소

(HbA

1C

)

의레벨은최근

3

개월간의 혈당조절을반영한다는점을고려하여투여기간이최소

12

^주^이

상인것으로제한하였다

.

또한용량별효과비교를위해

fixed- dose(Pioglitazone: 15 mg

또는

45 mg, Rosiglitazone: 4 mg

또 는

8 mg)

^로^투여한^연구만을^선정하고

dose titration

^이나

ranged-

dose

로투여한것은제외하였으며

, TZD

투여를금기로하는다

른질환이동반된환자

,

즉중증의심부전환자

(

뉴욕심장학회

(NYHA) class III~IV)

^이거나^활동성^간질환

,

^제

1

^형^당뇨

,

^당뇨

Fig. 1 −

Flow diagram of study selection

^.

(3)

병성케토산혈증

(ketoacidosis)

^등이^있는^환자에^대해서는^적절

한제외기준이명시되어있는논문으로제한하였다

.

^측정^변수

로는공복시혈당

(FPG),

당화혈색소

(HbA

1C

)

치의치료전후평 균과표준오차가명시되었거나

,

^산출^가능^한^것

(

^그^외^총^콜레

스테롤

, HDL, LDL,

중성지방과체중

,

혈압등은분석측정변수

이지만선정기준으로는하지않음

),

그리고한글

,

영어

,

일본어 중한가지로집필된것을선정하였다

.

질평가시행에있어서는

RCT

로서의타당성

,

방법론적유효성

,

무작위

,

맹검법

,

대조군설정등에대한적정성에대하여평가하 고선정여부를결정하였으며

, 2

^명의^연구자가^{독립적으로}^시행

하고불일치한부분은협의를통해확정하였다

.

개별논문들의효과크기로는치료전후의수치변화를해당 하는합병표준편차로나누어계산한

'

^표준화된^평균차

'

^를^사용

하였으며

,

통합효과크기는역분산가중법에의하여계산하였다

.

통합효과크기의산출시

,

동질성검정을시행하여동질성가설이 성립되는

(

^p

>0.1)

^군에^한하여

fixed effect model

^에^의해^효과

크기를추정하였으며

,

그외동질성가설이기각되는군에있어 서는

random effect model

^을^{적용하였다}

.

메타분석과정에서발생할수있는출판편견

(publication bias)

은

Pioglitazone

과

Rosiglitazone

의용량별공복시혈당

(FPG)

변

화에대해서 x축을효과크기로하고 y축을대상환자수로한깔 대기점도표

(funnel plots)

^를^그려^{평가하였다}

.

이연구의통계적분석에는윈도우용

Stata/SE 10.0

을사용하

였다

.

연구결과 및 고찰

논문검색결과

TZD

약물의

RCT 526

건이수집되었으며

,

이중

2

단계의전문검토를통해최종대상논문을선정하였다

(

총

57

건

, Pioglitazone 20

^건

, Rosiglitazone 39

^건

,

^중복

2

^건

)(Fig. 1).

^그리

고이논문가운데에는투여약물및용량별데이터를각각추 출할수있는논문이다수포함되어있었으며

,

이에각용량별 데이터에일련번호를부여한결과

,

^본^연구에^사용한^데이터는

Pioglitazone 27

개

, Rosiglitazone 51

개였다

(Table I).

혈당및심혈관계위험인자에대한 Pioglitazone의효과

Pioglitazone 15 mg

투여군에서각측정변수에대한효과크

기를산출한결과

,

^{신뢰구간에}

'0'

^을^포함하지^않아^유의성^있는

통합효과크기가구해진변수는

HbA

1C감소

(-0.762), FPG

^감소

(-23.365), TG

감소

(-29.792), HDL

증가

(4.633),

체중 증가 Table I

- Characteristics of the studies included

No Study

ID. Authors Year Prominent

Ethnic gr. Sample

size (n) Age (Year) Administration

mean s.d. Dose Duration Combination Pioglitazone

01 01 Aronoff et al.

⁵⁾

2000 western 0408 53.7 - 15 mg 26 wk none

0 02 45 mg 26 wk none

02 03 Bays et al.

⁶⁾

2007 western 1707 57.2 - 15 mg 24 wk none

04 55.7 - 45 mg 24 wk none

03 05 Belcher et al.

⁷⁾

2005 western 3713 57.0 09.4 45 mg 52 wk none

06 45 mg 52 wk none

07 45 mg 52 wk +su

08 45 mg 52 wk +met

04 09 Bluher et al.

⁸⁾

2003 other 0268 60.7 09.3 45 mg 26 wk none

05 10 Davidson et al.

⁹⁾

2006 western 0690 56.6 10.9 45 mg 24 wk +su

06 11 Derosa et al.

^{10; 11)}

2006 western 0091 53.0 06.0 15 mg 52 wk +met

07 12 Derosa et al.

¹²⁾

2007 western 0103 55.0 05.0 15 mg 52 wk +met

08 13 Forst et al.

¹³⁾

2005 other 0179 62.2 08.4 45 mg 24 wk none

09 14 Garber et al.

¹⁴⁾

2006 western 0463 54.8 10.6 45 mg 24 wk none

10 15 Gastaldelli et al.

¹⁵⁾

2007 western 0053 50.0 12.0 45 mg 16 wk +su

16 55.0 12.6 45 mg 16 wk none

11 17 Gerber et al.

¹⁶⁾

2003 western 0234 61.0 10.0 45 mg 20 wk none

12 18 Herz et al.

¹⁷⁾

2003 western 0297 59.0 11.0 45 mg 16 wk +met

13 19 Kipnes et al.

¹⁸⁾

2001 western 0560 56.5 09.8 15 mg 16 wk +su

14 20 Langenfeld et al.

¹⁹⁾

2005 western 0173 62.6 07.9 45 mg 24 wk none

15 21 Majima et al.

²⁰⁾

2006 Asian 0095 57.9 10.8 15 mg 24 wk +ins

16 22 Miyazaki et al.

²¹⁾

2002 western 0058 57.0 04.0 15 mg 26 wk none

23 55.0 02.0 45 mg 26 wk +ins

17 24 Scherbaum et al.

²²⁾

2002 other 0251 58.0 - 15 mg 26 wk none

18 25 Smith et al.

²³⁾

2005 other 0048 56.2 09.7 45 mg 24 wk none

19 26 Wallace et al.

²⁴⁾

2004 other 0030 61.4 27.5 45 mg 12 wk none

20 27 Watanabe et al.

²⁵⁾

2005 Asian 0027 62.9 10.3 15 mg 24 wk +met

(4)

(1.512),

혈압감소

(SBP: -4.004, DBP: -3.465)

였다

.

그리고통계

적유의성은없었으나

TC

^의^감소와

LDL

^감소가^관찰되어

,

^체 ^중을^제외한^모든심혈관계위험인자에서의효과가긍정적인것

으로평가하였다

(Table II).

Table I

- Continued No Study

ID. Authors Year Prominent

Ethnicgr. Sample

size (n) Age (Year) Administration

mean s.d. Dose Duration Combination Rosiglitazone

01 01 Albertini et al.

²⁶⁾

2007 western 0136 55.5 08.0 8 mg 12 wk none

02 02 Baksi et al.

²⁷⁾

2004 western 0473 61.1 09.1 8 mg 26 wk +su

03 03 Davidson et al.

²⁸⁾

2007 western 0245 52.0 11.9 8 mg 24 wk +su

04 04 Defronzo et al.

²⁹⁾

2005 other 0143 54.4 11.0 8 mg 12 wk none

05 05 Derosa et al.

^10;11)

2006 western 0091 54.0 05.0 4 mg 52 wk +su

06 06 Derosa et al.

³⁰⁾

2005 western 0099 54.0 04.0 4 mg 52 wk +met

07 07 Derosa et al.

¹²⁾

2007 western 0103 56.0 04.0 4 mg 52 wk +met

08 08 Fonseca et al.

³¹⁾

2000 western 0348 57.5 10.5 4 mg 26 wk +met

09 58.3 08.8 8 mg 26 wk +met

09 10 Freed et al.

³²⁾

2002 western 0243 60.0 10.0 8 mg 24 wk none

10 11 Gastaldelli et al.

¹⁶⁾

2007 western 0053 55.0 03.0 8 mg 16 wk none

11 12 Goldstein et al.

³³⁾

2003 western 1131 56.8 09.6 4 mg 26 wk none

13 58.8 10.0 4 mg 26 wk none

14 57.9 09.9 8 mg 26 wk none

15 59.1 09.8 8 mg 26 wk none

12 16 Gomez-Perez et al.

³⁴⁾

2002 other 0116 51.7 08.6 4 mg 26 wk +met

17 54.2 09.3 8 mg 26 wk +met

13 18 Hallsten et al.

³⁵⁾

2002 western 0045 58.6 02.0 8 mg 26 wk none

14 19 Hanefeld et al.

³⁶⁾

2007 western 0598 60.4 08.2 4 mg 52 wk none

20 60.6 09.2 8 mg 52 wk none

15 21 Jung et al.

³⁷⁾

2005 Asian 0027 60.0 08.0 4 mg 24 wk none

16 22 Kadoglou et al.

³⁸⁾

2007 western 0100 59.0 36.8 8 mg 32 wk none

23 57.8 37.3 8 mg 32 wk none

17 24 Kerenyi et al.

³⁹⁾

2004 western 0340 60.0 09.0 8 mg 26 wk +su

18 25 Kim et al.

⁴⁰⁾

2005 Asian 0125 58.8 08.8 4 mg 12 wk +su+met

19 26 Ko et al.

⁴¹⁾

2003 Asian 0136 61.6 08.2 4 mg 12 wk none

20 27 Lebovitz et al.

⁴²⁾

2001 western 0533 60.0 09.8 4 mg 26 wk none

28 61.0 09.5 8 mg 26 wk none

21 29 Miyazaki et al.

⁴³⁾

2001 western 0029 54.0 02.0 8 mg 12 wk none

22 30 Natali et al.

⁴⁴⁾

2004 western 0074 59.0 07.0 8 mg 16 wk none

23 31 Negro et al.

⁴⁵⁾

2005 western 0038 60.3 06.4 8 mg 52 wk +met

24 32 Patel et al.

⁴⁶⁾

1999 other 0380 59.7 10.0 4 mg 12 wk none

25 33 Phillips et al.

⁴⁷⁾

2001 western 0959 57.5 09.9 4 mg 26 wk none

34 58.9 09.9 8 mg 26 wk none

26 35 Rahman et al.

⁴⁸⁾

2007 Asian 0033 48.6 06.6 4 mg 52 wk none

27 36 Raskin et al.

⁴⁹⁾

2001 western 0319 57.1 10.0 4 mg 26 wk +ins

37 57.7 10.2 8 mg 26 wk +ins

28 38 Rosenstock et al.

⁵⁰⁾

2007 western 0786 54.2 11.6 8 mg 24 wk none

29 39 Seber et al.

⁵¹⁾

2006 other 0040 - - 4 mg 12 wk none

30 40 Sutton et al.

⁵²⁾

2002 other 0203 55.1 09.0 8 mg 52 wk none

31 41 Stocker et al.

⁵³⁾

2007 other 0092 64.0 11.0 4 mg 24 wk none

32 42 Viljanen et al.

⁵⁴⁾

2005 other 0037 58.6 07.7 8 mg 26 wk none

33 43 Vongthavaravat et al.

⁵⁵⁾

2002 other 0348 54.6 - 4 mg 26 wk +su

34 44 Weissman et al.

⁵⁶⁾

2005 other 0766 55.5 11.2 4 mg 24 wk +met

35 45 Wolffenbuttel et al.

⁵⁷⁾

2000 western 0593 61.0 09.4 4 mg 26 wk +su

36 46 Yang et al.

⁵⁸⁾

2002 Asian 0064 58.9 09.4 4 mg 24 wk none

37 47 Yilmaz et al.

⁵⁹⁾

2007 other 0066 57.6 08.8 8 mg 24 wk +ins

38 48 Yu et al.

⁶⁰⁾

2006 other 0072 61.9 07.9 4 mg 12 wk none

49 59.3 09.0 8 mg 12 wk none

39 50 Zhu et al.

⁶¹⁾

2003 Asian 0530 59.0 07.5 4 mg 24 wk +su

51 58.9 06.9 8 mg 24 wk +su

*met: metformin, su: sulfonylurea, ins: insulin

(5)

Pioglitazone 45 mg

^투여^군에서도

HbA

1C

, FPG, TG

^의^감소

와

, HDL

^증가

,

^체중^증가

,

^혈압^감소가^{관찰되었으며}

, TC

^와

LDL

은

15 mg

투여시와는반대로약간증가하는것으로나타났다

.

혈당및심혈관계위험인자에대한Rosiglitazone의효과

Rosiglitazone 4 mg

투여군에서각측정변수에대한효과크기 Table II −

Comparison of the effect sizes: Pioglitazone versus

Rosiglitazone

Medication Variable No Pooled

effect size 95%CI Lower Upper Comparison between low-dose-administered groups

Pio 15 mg HbA

1C

09 -0.762 -1.096 -0.428

Rosi 4 mg 18 -0.833 -1.096 -0.569

Pio 15 mg FPG 09 -23.365 -31.902 -14.829

Rosi 4 mg 15 -34.059 -40.137 -27.982

Pio 15 mg TC 08 -3.072 -9.571 3.426

Rosi 4 mg 18 17.939 14.146 21.731

Pio 15 mg LDL 08 -2.037 -7.853 3.780

Rosi 4 mg 18 10.327 6.455 14.200

Pio 15 mg TG 08 -29.792 -38.666 -20.918

Rosi 4 mg 17 6.920 -2.047 15.888

Pio 15 mg HDL 08 4.633 3.680 5.585

Rosi 4 mg 19 3.432 2.646 4.218

Pio 15 mg Weight 03 1.512 1.185 1.839

Rosi 4 mg 05 0.103 -1.495 1.701

Pio 15 mg SBP 04 -4.004 -5.188 -2.819

Rosi 4 mg 07 -3.523 -4.960 -2.086

Pio 15 mg DBP 04 -3.465 -4.480 -0.688

Rosi 4 mg 07 -2.552 -4.152 -0.951

Comparison between high-dose-administered groups Pio 45 mg HbA

1C

13 -0.919 -1.173 -0.665

Rosi 8 mg 17 -1.027 -1.284 -0.770

Pio 45 mg FPG 11 -34.774 -47.608 -21.941

Rosi 8 mg 18 -35.802 -40.267 -31.336

Pio 45 mg TC 11 3.274 -1.317 7.866

Rosi 8 mg 14 19.727 15.202 24.253

Pio 45 mg LDL 11 2.324 -1.967 6.616

Rosi 8 mg 14 14.332 11.415 17.250

Pio 45 mg TG 11 -33.658 -50.736 -16.581

Rosi 8 mg 14 4.636 -4.554 13.827

Pio 45 mg HDL 11 5.532 4.394 6.671

Rosi 8 mg 14 4.708 3.730 5.687

Pio 45 mg Weight 09 2.610 2.060 3.159

Rosi 8 mg 07 3.217 2.056 4.377

Pio 45 mg SBP 03 -5.240 -10.492 0.012

Rosi 8 mg 06 -2.103 -4.547 0.340

Pio 45 mg DBP 03 -2.463 -4.029 -0.898

Rosi 8 mg 06 -2.588 -4.099 -1.077

Pio: Pioglitazone

Rosi: Rosiglitazone

^{Fig. 2 −}

Forest plots of comparison between low-dose-administered

groups: Pioglitazone 15 mg versus Rosiglitazone 4 mg

.

(6)

를산출한결과

,

^{신뢰구간에}

'0'

^을^포함하지^않는^{통합효과크기가}

구해진변수중

,

^긍정적인^효과로는

HbA

1C감소

(-0.833), FPG

감소

(-34.059), HDL

증가

(3.432),

혈압감소

(SBP: -3.523, DBP:

-2.552)

^가^있었다

.

^그리고^부정적인^효과로는

TC

^증가

(17.939)

^와

LDL

의증가

(10.327)

가있었다

(Table II).

Rosiglitazone 8 mg

를투여한군에서도

4 mg

투여시와유사 한경향을보였고

,

^이들^{통합효과크기는}

4 mg

^투여^시보다^증가

하는것으로나타나

,

투여용량증가시그효과가커짐을알수 있었다

.

Pioglitazone과Rosiglitazone의효과비교

두약제의효과비교를위해

Pioglitazone

과

Rosiglitazone

의 각측정변수에대한통합효과크기를저용량및고용량에서각각 비교하였다

(Table II).

두약물의저용량투여군에서통계적으로유의한통합효과크 기를비교할수있었던항목은

HbA

1C감소

(pio15: -0.762, rosi4:

-0.833), FPG

감소

(pio15: -23.365, rosi4: -34.059), HDL

증가

(pio15: 4.633, rosi4: 3.432)(Fig. 2), SBP

^감소

(pio15: -4.004, rosi4: -3.523), DBP

^감소

(pio15: -3.465, rosi4: -2.552)

^였다

.

^그

리고

TC, LDL, TG

의혈중농도는

Pioglitazone 15 mg

투여군 에서감소하였고

, Rosiglitazone 4 mg

투여군에서는이와반대 로증가하였다

.

고용량투여군에서통계적으로유의한통합효과크기를비교할 수 있었던 항목은

HbA

1C 감소

(pio45: -0.919, rosi8: -1.027), FPG

^감소

(pio45: -34.774, rosi8: -35.802), HDL

^증가

(pio45:

5.532, rosi8: 4.708)(Fig. 3),

체중 증가

(pio45: 2.610, rosi8:

3.217), DBP

^감소

(pio45: -2.463, rosi8: -2.588)

^였다

.

^그 ^외

triglyceride

^의^혈중^농도는

Pioglitazone 45 mg

^투여^군에서는^감

소하고

, Rosiglitazone 8 mg

투여군에서는반대로증가하는것 으로나타났다

. TC

^와

LDL

^은^저용량^투여군^비교^시와는^달리

두 약제에서모두 증가하였다

(TC

^와

LDL

^이 ^증가한 ^정도는

Rosiglitazone

이더욱컸다

).

출판편견(Publication bias)의평가

Pioglitazone

과

Rosiglitazone

의용량별공복시혈당

(FPG)

변 화에대해서 x축을효과크기로하고 y축을대상환자수로한깔 대기점도표

(funnel plot)

를그려출판편견을평가하였다

.

그결과

,

전체적으로연구결과의효과크기분포가통합효과크기를중심으 로약간의비대칭성을보였다

(Fig. 4).

고찰 및 결론

메타분석은

Glass(1976)

에의해개발된이래로의약분야에도

도입되어기존 종설

(review article)

에의한 연구의종합방법이

Fig. 3 −

Forest plots of comparison between high-dose-administered

groups: Pioglitazone 45 mg versus Rosiglitazone 8 mg

.

(7)

지니는주관성의한계를보완하는기법으로널리이용되고있다

.

이연구는이러한메타분석방법을적용하여두

TZD

약물의효 과를종합적으로비교한결과라고볼수있다

.

이연구에서는

Egger(1997)

가제시한여러선택편의중

,

연구

과정에서배제하기어려운출판편의

(publication bias)

^를^제외하

고는분석진행과정에서이의배제를위해필요한절차를강구하 였다

.

먼저

,

연구과정에서인용편의

(citation bias)

를배제하기위 해연구대상선정시영문및국문으로출판된문헌의검색과 정에서접근이가능한모든방법을동원하였다

.

^또^{중복출판에}

의한편의

(multiple publication bias)

를배제하기위해동일집단 을대상으로여러편의논문이발간된경우에는시기적으로최 근에발표된논문

1

^편만을^대상으로^하고^나머지는^{제외하였다}

.

잠재적편의의평가방법으로채택한

funnel plot

상의약간의

비대칭성은효과크기가더큰영역에서도결손부위가나타나그 원인이출판편견이라기보다는이영역에서의연구가충분히이 루어지지않았기때문으로판단하였다

.

연구결과는다음과같다

.

첫째

, Pioglitazone

이심혈관계위험인자에미치는효과는혈

당치와

triglyceride

감소

, HDL

증가

, SBP

와

DBP

의감소의측 면에서긍정적이었으며

,

^부정적인^효과로는^고용량^투여^시의

total cholesterol

증가와

LDL

의상승

,

체중증가등이있었다

.

둘째

, Rosiglitazone

^투여^시에는^모든^용량에서

HbA

1C 와혈 당치가뚜렷한감소를보인반면

,

^혈중지질

(TC, LDL, TG, HDL)

이모두증가하였다

.

셋째

,

^저용량과^고용량^모두에서^{혈당강하효과는}

Rosiglitazone

이다소컸던반면

,

^{지질조절에}^대한^효과는

Pioglitazone

^이^더

욱좋은것으로평가하였다

.

그리고체중증가의정도는두약제 가비슷했으며

,

^혈압강하^효과는

Pioglitazone

^이^다소^컸다

.

Elaine Chiquette

^의^선행연구⁴⁾^와의^비교^시

,

^이^연구는^그^이

후에축적된연구결과들을포함시켜주요심혈관계위험인자인 혈압과체중변화에대해서도통합적인효과를추정하였다는점

,

단일용량투여의시험만을사용하여용량별로효과의차이를비 교하였다는점

,

그리고두약제의효과에대한직접적인비교를 시도하였다는점등에서차이가있다

.

^또한^두^{연구결과를}^비교

Fig. 4 −

Funnel Plots.

(8)

해보면

,

^두^약제^모두에서^혈당강하^효과가^{뚜렷하다는}^점과^지

질조절효과가

Pioglitazone

^에서^더욱^{긍정적이라는}^점은^일치하

였지만

,

본연구에서는

Rosiglitazone

에서

HDL

의상승이외에는 긍정적인지질조절효과가관찰되지않아그결과가더욱보수적 이라고볼수있었다

.

이연구는두

TZD

약물이당뇨환자의심혈관계위험인자에

미치는효과에있어서그차이점을함께제시함으로써개별환

자의혈중지질농도

profile

에따른적절한약제의선택을가능

하게했다는점에서의의가있다

.

하지만

, TZD

약물의여러가

지효과를보다정확하게추정비교하기위해서는향후보다질 높은임상시험이선행되어야할것으로보인다

.

감사의 말씀

본연구는

2008

년도숙명여자대학교학술연구지원비에의해

수행되었으므로이에감사드립니다

.

참고문헌

1)

^{한국보건사회연구원}

: 2001

^년도^국민건강^영양조사

-

^{만성질병편}

,

보건복지부

(2002).

2)

^{대한의사협회}^{의료정책연구소}

:

^보건의료^통계^분석

-OECD

^보건

통계 자료를 기초로

-Analysis of the OECD Health Data 2006,

연구보고서 제

2007-3

호

, pp. 32-33 (2007).

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(9)

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