???,??33??,??????12?,??????????,???????glibenclamide 10 mg BID Metformin 1000mg BID Amlodipine 10mg QD,???????????,?????????????????????,????????????????????,???????????,??????????,?????,?????????????????????????,??????????1800??/??

1
????????(??)-??
???-1

• ????? ???
• ? ? ?? ? ?

??????????????????
2
??

• ???,??33??,??????12?,??????????,???????glibencl
  amide 10 mg BID Metformin 1000mg BID
  Amlodipine 10mg QD,???????????,???????????????????
  ??,????????????????????,???????????,??????????,???
  ??,?????????????????????????,??????????1800??/??

3
????????

• ??????161??,??54.3??,????57??,BMI
  20.9,??140/90 mmHg,???????????????,??????????,????
  ????????
• ?????AC Sugar 196 mg/dL,A1C 8.5,TC 218
  mg/dL,HDL 32 mg/dL,LDL 121 mg/dL,TG 307 mg/dL,
  CRE 1.0 mg/dL,GPT 22 mg/dL,urine protein
  (),Albumin/Creatinine 296.3 mg/g,
• ????????

4
??

• ?????????
• ?????????
• ??????????
• ??????????????
• ????????????

5
?????????

• ???????????
• (1)????Insulin -----------------------( )
• (2)????Acarbose -------------------( )
• (3)????Glitazones ------------------( )
• (4)????????---------------------( )
• (5)????????---------------------( )
• (6)??????????---------------( )

6
?????????

• ???????????
• (1)????Insulin -----------------------(O)
• (2)????Acarbose -------------------(?)
• (3)????Glitazones ------------------(O)
• (4)????????---------------------(?)
• (5)????????---------------------(O)
• (6)??????????---------------(?)

7
?2??????????

• ??????????,??????,??????????(?????????),?????????2
  0-40U,??????????100-200U ?
• ?????gt 40U,???????,?????2/3??,1/3??(??????)?
• ???????,?????????????
• ???????????????????????????(????100U )

8
?????????????????????

• ??????????(???????????,???????????????)
• BMIlt25?/?,?????? 5-10 U NPH (????Mixtard
  70/30),??0.15U/ ???
  BMIgt25?/?,??????10-15 U NPH (????Mixtard
  70/30)
• ???????(??2-3???,?????)
  ???? gt140mg/dl,??4?????
• ???? 110-140mg/dl,??2?????
• ???? lt80mg/dl,??4?????

9
?????????????????
?? ???? ???A1C A1C ?? ??
Shank NPH hs Placebo Glipizide NPH hs Glipizide 8.5 8.2 8.9 -0.7 0.2 -1.8 ?????????
Landstedt- Hallin RI Glyburide NPH hs 9.2 -2.1 -1.7 ?????????
Riddle Sxhneider Insulin Placebo Insulin Glimepiride 9.9 9.7 -2.2 -2.1 Glimepiride????????????????
10
?????????????????
?? ???? ???A1C A1C ?? ??
Giugliano Insulin Placebo Insulin Metformin 11.5 11.7 -0.2 -1.9 ?????????
Coniff Insulin Placebo Insulin Acarbose 6.6 6.4 -0.2 -0.6 Acarbose???????
Raskin Graveline Insulin Placebo Insulin TZD 200mg Insulin TZD 600mg 9.43 9.51 9.32 -0.1 -0.8 -1.4 ?????? ???TZD
11
?2????????????????????
????? ?? ????
A1C
7
Turner RC et al. JAMA. 19992812005-2012.
12
???2????????????????????
????? ?? ????
A1C
7
Turner RC et al. JAMA. 19992812005-2012.
13
?2???????????????
A1C FBG (mg/dL)
Sulfonylurea Metformin Pioglitazone Rosiglitazone Repaglinide Acarbose 1.5 to 2 1 to 2 0.6 to 1.9 0.7 to 1.8 0.8 to 1.7 0.5 to 1.0 50 to 60 50 to 60 55 to 60 55 to 60 30 to 40 20 to 30
14
?2???????????????
A1C FBG (mg/dL)
Sulfonylurea Metformin Sulfonylurea Pioglitazone Sulfonylurea Acarbose Repaglinide Metformin Pioglitazone Metformin Rosiglitazone Metformin 1.7 1.2 1.3 1.4 0.7 0.8 65 50 40 40 40 50
15
Rosiglitazone ???????
Compared to Baseline
Compared to Placebo(Treatment Effect)
1.5
0.9
1.0
0.5
0.0
Change in Mean HbA1c ()
-0.5
-0.3
-1.0
-0.6
-1.5
-1.2
-2.0
-1.5
Placebo
4 mg
8 mg
4 mg
8 mg
Plt0.0001 Plt0.0045 Patel, et al. Diabetes.
199847(Suppl 1)A17.
16
Sulfonylurea - rosiglitazone ????
1
?0.6
0
Change of Mean HbA1c ()
?0.3
?1
4 mg QD
Gly Placebo
?2
Placebo-adjusted ? at 4 mg ?0.9
Schneider, et al. Diabetes. 199948(suppl
1)A106 Avandia (rosiglitazone) package insert
4/00.
17
Repaglinide-rosiglitazone????
???????
A1C
??
mg/dl
250 participants with type 2 diabetes
inadequately controlled by previous oral therapy
with sulfonylureas or metformin A1C 9.1 at
baseline
18
Nateglinide-rosiglitazone????
?????
A1C
??
mg/dl
402 type 2 DM patients 24-week study ,Starlix
(120 mg, before a meal) and placebo added to
ongoing open label rosiglitazone (8 mg, q.d.)
baseline A1C 8.3
19
Metformin-rosiglitazone????
???????
A1C
??
mg/dl
119
113
119
113
348 patients aged 40 to 80 years with a mean
fasting plasma glucose 216 mg/dL, A1C 8.8, and
a mean BMI 30.1 kg/m2 were randomized
20
Insulin- rosiglitazone ????FDA Approves Doctor's
Guide March 3, 2003

• ??26????2 ????????,
• ????1,100 ?
• Rosiglitazone 4 mg qd ??????????????
• ??4 mg bid???40 ????????

21
Glitazones ???????GPTgt3X
48/2510
2/793
4/1526
13/4500
22
?????????Troglitazone Metformin Sulfonylurea
TGZ M S PBO M S
FPG (mg/dL) -43 5
HbA1c -1.3 0.1
Total Insulin (?U/mL) -2.5 0.8
Triglycerides (mg/dL) -26 41
Randomized, placebo-controlled study in 178
patients with type 2 diabetes Troglitazone (TGZ,
400 mg QD) or placebo (PBO) added to maximal
tolerated dosages of metformin (M) or a
sulfonylurea (S) for 6 months
pioglitazone ? rosiglitazone ?2002???metformin?sul
phonylurea???????
23
Triple Oral Therapy in Type 2 Diabetes
Glimepiride Metformin Troglitazone
12
Plt0.01 from baseline
11
10




9

• HbA1C

8
7
6
5
4
0
2
3
4
5
6
1
Time (Months)
Ovalle F and Bell DSH. Endocr Pract.
19984146-147.
24
A Desktop Guide to Type 2 Diabetes IDF (Europe)
1999

• Add another agent of therapy when maximum dose of
  current drugs reached
• Use triple therapy when control targets cannot be
  reached on maximum tolerated doses of two agents

Joslin diabetes center ??triple therapy ???
UK ?????????ROSI/PIO MET SU?????.This is
currently off-licence, but details from recent
symposia are reassuring
25
NICE Guidance on Rosiglitazone

• ??????????????
• ?????????(????????)????????????????????,??????????
  ?
• ??????????(????????)??????????Rosiglitazone???????
  
• ????????????????????????????,?????????,???Rosiglit
  azone ?????????????????
• ??????Rosiglitazone?????,????????,????????????

NICE - The National Institute for Clinical
Excellence - was set up as a Special Health
Authority for England and Wales. It is part of
the National Health Service (NHS), and its role
is to provide patients, health professionals and
the public.
26
Oral triple therapy or add insulin?

• ??????????????????????
• ??????????????????2 ?????????????
• ????????????????,?????????,?????????
• ?2 ??????????A1C?? (9.7),????????A1C????lt6,?????
  ?????????????,??????????????????,????????

27
?2??????????????

• HbA1c ??????????????
• ???????
• ????????
• ??????????
• ???????
• ???????????
• ??????????
• ??

5-1a
28
????????????
Rosiglitazone
91/5/23 91/8/15 91/11/13 92/3/7 92/6/5
BW 57.6 56.7 58.4 58.7 57
AC 196 173 195 129 138
A1C 8.5 9.1 8.5 6.4 7.1
GPT 22 21
29
???????????
30
???????????
31
?????????

• ???????????
• (1)????ACE???-------------------( )
• (2)????ARB ---------------------------( )
• (3)????Adalat -------------------------( )
• (4)????????----------------------( )
• (5)????????----------------------( )
• (6)???????120/80 mmHg -----( )

32
?????????

• ???????????
• (1)????ACE???-------------------(O)
• (2)????ARB ---------------------------(O)
• (3)????Adalat -------------------------(X)
• (4)????????----------------------(O)
• (5)????????----------------------(O)
• (6)???????120/80 mmHg -----(O)

33
Blood Pressure-????????
???????????? ??? ???
?? ??????(?????) ????????? ?????????? lt130 130-139 ?140 lt80 80-89 ?90
34
Blood Pressure-??????????
???? ?? ????
?? ???????? ?10?? 520 mmHg
DASH ???????????? 814 mmHg
???? 2.4???6.0???? 28 mmHg
???? ??????30?? 49 mmHg
???? ?????2?,??1? 24 mmHg
35
Blood Pressure-????????Dietary Approaches to
Stop Hypertension??????2000Kcal??,??????????????
???? ??? ??? ??????
??? ??? 78?/? 15? 1????1????? 1/2??????????
??? 45?/? 3? 1???????? 1/2??????180ml???
??? 45?/? 2? 1??????1/4???? 1/2??????????
???? ???? 23?/? 1? 240ml???1????45g??
36
Blood Pressure-????????Dietary Approaches to
Stop Hypertension??????2000Kcal??,??????????????
???? ??? ??? ??????
??,????? 2??2? ??/? 6? 90g???????????
??? 45?/? 1/3?(?45g )???1??(?15g )?? ½??????
??? 23?/? 6? 1?????????1??????? 2????????1?????
?? 5?/? 1????1???? 15g???240ml???
37
Blood Pressure-????????????ESHESC

• ??????,????2????????????(??????????)
• ????????lt130/80mmHg
• ??????????
• ?????1??????ACE inhibitors??2??????ARB????????
• ?????????????????,?????ß-blockers?ACE inhibitors?
  ARB
• ?1???2??????????????????, ACE inhibitors? ARB

38
Blood Pressure-??????????????(JNC7)

• ?????????????????????lt130/80 mmHg
• Thiazide ????ßblockers?CCBs?
• ACE inhibitors?ARB???????????????????
• ACE inhibitors?ARB????????????????
• ARB??????????

39
?????????

• TC 218 mg/dL
• HDL 32 mg/dL
• LDL 121 mg/dL
• TG 307 mg/dL

40
??????????

• ???????????
• (1)????Statins ------------------------( )
• (2)????Fibrates -----------------------( )
• (3)??????Niacin -------------------( )
• (4)??????????????----( )
• (5)????????----------------------( )

41
??????????

• ???????????
• (1)????Statins ------------------------(O)
• (2)????Fibrates ----------------------(O)
• (3)??????Niacin -------------------(X)
• (4)??????????????----(O)
• (5)????????----------------------(O)

42
?????????
91/5/23 91/8/15 91/11/13 92/3/7
A1C 8.5 9.1 8.5 6.4
TC 218 201 288 279
HDL 32 38 40 38
LDL 121 119 197 204
TG 307 338 253 139
43
??????????

• ???????????
• (1)????Statins ------------------------( )
• (2)????Fibrates -----------------------( )
• (3)????????????-----------( )
• (4)?????????? ----------------( )
• (5)????????-----------------------( )

44
???????????????
?? LDL HDL TG
? ?130 lt35 ?400
?? 100-129 35-45 200-399
? lt100 gt45 lt200
45
???????LDL??????
???? ???? ???? ????
??? LDL ??? ??? LDL ???
?CHD?PVD?CVD gt100 ?100 gt100 ?100
??CHD?PVD?CVD gt100 ?100 ?130 ?100
46
??????????????

• ???????????
• (1)??????--------------------------( )
• (2)??????--------------------------( )
• (3)???????-----------------------( )
• (4)????--------------------------------( )
• (5)????--------------------------------( )
• (6)????--------------------------------( )
• (7)?????Aspirin--------------------( )

47
??????????????

• ???????????
• (1)??????--------------------------(O)
• (2)??????--------------------------(O)
• (3)???????-----------------------(O)
• (4)????--------------------------------(O)
• (5)????--------------------------------(O)
• (6)????--------------------------------(O)
• (7)?????Aspirin--------------------(O)

48
Evidence Base Medicine-???
?? ??
????????????????????? E
???????????????????????????? E
???????metformin,TZD?????,????????????????????????????? E
49
Evidence Base Medicine-????
?? ??
???????????????Aspirin(75-325 mg/day) A
40??????????????????,???Aspirin????? A
lt21????Aspirin,????Reyes??? A
30-40?????????????Aspirin?? B
50
Evidence Base Medicine-??
?? ??
?????????? A
??????????????????????????? B
51
????????????

• ???????????
• (1)??????-------------------------------( )
• (2)??????-------------------------------( )
• (3)???????----------------------------( )
• (4)???????????????----( )
• (5)??????0.6??/????--------( )

52
????????????

• ???????????
• (1)??????-------------------------------(O)
• (2)??????-------------------------------(O)
• (3)???????----------------------------(O)
• (4)???????????????----(X)
• (5)??????0.6??/????--------(X)

53
??????-?????????
54
Evidence Base Medicine-???
?? ??
?????????????,?????? A
?????????????,?????? A
?1???????5?????2???????,??????????? E
????????ACE????ARB A
???????????0.8??(????10),?GRF????????????? B
55
Evidence Base Medicine-???
?? ??
DCCB???????????????????ARB? B
GFRlt60ml/min/1.73m²?????????????,???? B