1130820-家醫群家醫計畫2.0-實體+線上-社團法人高雄市醫師公會.pdf

基層DKD整合照護計畫分享
1
晶品診所
陳重元
2024-8-20

3

4

台灣第2型糖尿病患合併腎病變人數及比率皆逐年攀升
5
中華民國糖尿病衛教學會 , 臺灣糖尿病年鑑 2019第2型糖尿病簡報
http://www.endo-
dm.org.tw/DB/book/73/%E8%87%BA%E7%81%A3%E7%B3%96%E5%B0%BF%E7%97%85%E5%B9%B4%E9%91%91%202019%E7%AC%AC2%E5%9E%8B%E7%B3%96%E5%B0 %BF%E7%97%85%20%E7%B0%A1%E5%A0%B1.pdf
2000-2014臺灣T2D合併CKD
比率+95.4%，人數+407%
2011 年啟動初期慢性腎
臟病給付改善方案

糖尿病患合併心衰竭或腎病變的死亡風險增加
a.Standardized according to a model adjusted for age, sex, and race
1. Diabetes Care2004 Mar;27(3):699-703. ；2. Afkarian M et al. J Am Soc Nephrol2013;24:302–308
糖尿病患罹患心衰竭，死亡風險增加10倍
Years
Proportion surviving
Diabetes with heart failure
(n=46,720)
Diabetes, without heart failure
(n=69,083)
HR: 10.6 P<0.001
11.5
31.1
0
5
10
15
20
25
30
35
40
Standardized cumulative incidence
(%)
Diabete
s
Diabetes with kidney
disease
~3
x
糖尿病患罹患腎病變，死亡風險增加3倍
The NHANES is a population-based program of studies conducted by the National Center for Health
Statistics of the US Centers for Disease Control and Prevention.This study uses data from NHANES III
participants aged ≥ 20 years.
Ten-year standardized all-cause mortality, by diabetes and kidney disease status
2,a
Study design:
A national, nonconcurrent
cohort study of U.S. elders with diabetes
by using data from the 5% standard analytical file, which contained Medicare
claims for 1,941,453 individuals in 1994

導致ESRD的主因為糖尿病
ESRD: End-Stage Renal Disease Unknown cause incluses polycystic kidney disease, among other cause.
1. US CDC. Chronic Kidney Disease in the United States, 2019.
Cause of ESRD
Diabetes
No. 1
No. 2Hypertension
No. 3 Glomerulonephritis
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8

加上國人腎臟病識能缺乏與錯誤
可能導致延誤就醫或疾病惡化
1. Formos Med Assoc. 2019 Nov;118 Suppl 2:S122-S129. (Participants in P4P).;
2.衛福部國健署 _ https://www.hpa.gov.tw/Pages/Detail.aspx?nodeid=4576&pid=15084;
3. 台灣基層糖尿病協會 2020年及時篩腎心安計畫調查結果
P4P=pay-for-performance ; HPSS=ROS Proto-Oncogene
2成的人不知驗尿檢查腎功能
5成不知血壓未控好會引起腎臟病
2成不知血糖未控好會引起腎臟病
國民健康署 2018年健康促進業務
推動現況與成果調查 (HPSS)
18歲以上的成人中
2
台灣基層糖尿病協會
2020年
【及時篩腎心安2.0】計畫
3
未察覺
出現尿蛋白
篩檢期間 : 2020年4月~2020年10月
計畫涵蓋 102 家全台基層診所
51,283 名糖尿病患
元成診
9

微量蛋白尿是腎臟出現異常的重要警訊
2
然而臨床關注度仍舊不足
1. J Am Coll Cardiol 2013;61:1626–1633; 2.中華民國糖尿病衛教學會 , 臺灣糖尿病年鑑 2019第2型糖尿病_簡報
2. DeFronzo RA.Diabetes Reviews. 1995 Jan 1;3(3):510-564.
UACR=urine albumin to creatinine ratio ; T2D=type 2 diabetes
Adjusted all-cause mortality
according to UACR at baseline in
patients with and without diabetes
1
第2型糖尿病患者
每年接受 UACR 尿液常規
及血清肌酸酐檢查之比率
2
AstraZeneca has no intention to promote its drugs outside of it approved indications.
10

隨著腎功能的下降
患者健康相關生活品質將大受衝擊
Stage 5D, dialysis; stage 5T, transplant.
Kalantar-Zadeh, K., Lockwood, M.B., Rhee, C.M. et al. Patient-centred
approaches for the management of unpleasant symptoms in kidney
disease. Nat Rev Nephrol 18, 185–198 (2022).
https://doi.org/10.1038/s41581-021-00518-z
The burden of unpleasant symptoms
across progressive stages of chronic kidney disease
11
照護及衛教
也將變得更為複雜不易
元成診所
11

CKD患者不僅透析風險增加
死亡風險也大幅增加
Arch Intern Med. 2004 Mar 22;164(6):659-63.
10.2
19.5
24.3
45.7
0.06
0.9 1.1
17.6
0
5
10
15
20
25
30
35
40
45
50
GFR, 60-89;
No Proteinuria
Stage 2
GFR, 60-89; Proteinuria
Stage 3
GFR, 30-59
Stage 4
GFR, 15-29
Mortality Initiated dialysis
%
N= 14,202 N= 1,741 N= 11,278 N= 777
27,998 patients with 5-year observation
period in the US from 1996 to 2001
12
Risk:Mortality>>ESRD
因此除了延緩透析
降低死亡風險
也是CKD治療重要的目標
元成診所
12

13
•糖尿病(DM) since 民國90年
•早期腎病變 (early CKD, pre ESRD) 民國100年
•DM + early CKD = DKD 民國111年
•MS 民國111年(Prediabetes民國112年)
•家醫2.0計畫民國113年
強化基層醫療的照護

14

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16
•U-total protein(TP) 09040C 40點
•U-Cr. 09016C 40點
•U-albumin 12111C 275點
•CKD(非糖尿病人 )驗U-TP 和U-Cr.組合成U-PCR(protein Cr
ratio)正常<150
•糖尿病人驗 U-albumin和U-Cr.組合成U-ACR(albumin
creatinine ratio)正常<30
單次尿液U-PCR, U-ACR 半年可以驗一次

17
•建議同時測 urine routine,因urine WBC和RBC 數值，
UTI和血尿都會影響 protein 和albumin。
一般U protein 1+ >300，DM不管>1000, 依然check U-ACR

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如何做
飲食
運動
監測
藥物
21

最新2023年ADA第2型糖尿病藥物治療流程圖
Diabetes Care Volume 46, Supplement 1, January 2023,S147
ASCVD
HF
CKD
HbA1C
Weight
延續2022 年ADA/EASD共識
強調全方位血糖管理與心腎保護
ASCVD:
Atherosclerotic
cardiovascular
disease動脈粥狀硬
化心血管疾病。定
義：曾患急性冠心
症或心肌梗塞，穩
定或不穩定心絞痛，
冠狀動脈疾病 (包括
無或有血管再通術 )，
其它動脈血管再通
術，中風，或動脈
粥狀硬化引起的周
邊動脈疾病

2023 ADA糖尿病治療指引：
選擇對心血管和腎臟有好處的藥物
*Risk reduction interventions to be applied as individually appropriate Adapted from 2022 ADA guideline Diabetes Care
2022;45(Suppl. 1):S144-S174.
生活習慣調整與糖尿病衛教
血糖控制血壓控制血脂控制
對心血管和腎臟
有好處的藥物 *
減少糖尿病併發症
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TW-23170 _FOR_14/02/2023
24
ADA最新糖尿病照護指引
首選具心腎實 ? SGLT2i
Diabetes Care Volume 46, Supplement 1, January 2023,S147
優先使用
有延緩慢性腎病進程主要實 ? SGLT2i
在eGFR ≥ 20ml/min per 1.73 m
2
可使用SGLT2i ，一
旦開始就應該持續至開始透析或換腎時
(使用ACEi/ARB到可容忍之最大劑量 )
假如SGLT2i不適用，可選擇有心血管實 3
GLP-1 RA
——或——
慢性腎臟病
eGFR< 60
ml/min per 1.73 m
2
UACR≥30
mg/g或目標:
降低患有第2型糖尿病之
(心腎)高風險病人之心腎風險
(在全面的心血管風險管理之下 )
目標: 達成及維持
血糖與體重控制目標
生
活
型
態
與
自
我
管
理
AstraZeneca does not recommend the use of drugs outsides of it approved indications

TW-23170 _FOR_14/02/2023
25
中華民國糖尿病學會
2022第2型糖尿病臨床照護指引
建議優先使用 SGLT-2抑制劑
(建議強度 :強烈)
或
UACR≥30
mg/g
eGFR<60
ml/min/1.73m
2
http://www.endo-dm.org.tw/dia/
臨床建議

Overview of SGLT2i in Renal Outcome Trials
26
Please note that as head-to-head studies were not conducted between these products, it is inappropriate to draw any comparisons and/or make any conclusions as the study design, demographics and other criteria may be different.
CKD trial
Renal composite primary
endpoint
hHF/
CV death
Total
death
Dapa
-39%
P=0.000000028
-29%
p=0.009
-31%
p=0.004
Empa
-28%
HR 0.84
(0.67–1.07)
HR 0.87
(0.70–1.08)
Cana
-30%
(only DM)
p=0.00001
-31%
(only DM)
p<0.001
HR 0.83
(0.68–1.02)
(only DM)
Ertu
N/A N/A N/A
Sota
Renal composite outcome
HR 0.71
(0.46-1.08)
(only DM)
-26%
(only DM)
p<0.001
HR 0.99
(0.83-1.18)
(only DM)
1.N Engl J Med. 2020 Oct 8;383(15):1436-1446.2. Late Breaking session at ESC Congress 2020 -The Digital Experience. 29 Aug -01Sep presented by Hiddoet al.3. N Engl J Med. 2019 Jun 13;380(24):2295-2306. 4.N Engl J Med. 2021 Jan 14;384(2):129-139. 5. N
Engl J Med. 2023 Jan 12;388(2):117-127
: significant reduction: not significant

CKD患者使用Forxiga
Ⓡ
可有效減緩 eGFR下降速度54%，遠離洗腎
-1.67 ml/min/1.73 m
2
per year
-3.59 ml/min/1.73 m
2
per year
約13-14個月
27
Baseline eGFR 43
97% with RASi
Age 62 years
1.92
ml/min/1.73 m
2
per year
( 95%CI, 1.61 to 2.24 )
2020年
27

TW-23170 _FOR_14/02/2023
28
FORXIGA提供T2D患者從預防到治療CKD完整實
ESRD ↓ 69%
HR 0.31 (0.13-0.79),
p=0.013
HR 0.53 (95%CI 0.43-0.66)
p<0.0001*
Renal composite outcome
sustained ≥40% eGFR decline to <60 mL/min/1.73 m
2
, ESKD, or
renal death
針對9成eGFR≥60且近7成UACR<30 mg/g的
T2D患者使用 Dapagliflozin10 mg
*Nominally significant, prespecified exploratory outcome; Renal composite outcome: sustained ≥40% eGFR decline to <60 mL/min/1.73m2, ESKD, or renal death
1. N EnglJ Med. 2019 Jan 24;380(4):347-357. 2. Lancet Diabetes Endocrinol. 2019 Aug;7(8):606-617.3. Diabetes ObesMetab. 2020 Aug;22(8):1357-1368.4.N
EnglJ Med. 2020 Oct 8;383(15):1436-1446
0
HR (95% CI) p-value
0.61 (0.51-0.72) 0.000000028
2152 1993 1936 1858 1791 1664 1232 774 270Placebo
FORXIGA 10 mg
197 events
Placebo
312 events
2152 2001 1955 1898 1841 1701 1288 831 309FORXIGA 10 mg
4
8
12
16
20
24
0 4 8 1
2
1
6
2
0
2
4
2
8
3
2
Months from Randomization
Cumulative Incidence %
N at Risk
composite of a sustained decline in the eGFR ≥50%, ESRD, or death
from renal or CV causes
Primary outcome
ESRD ↓ 36%
HR 0.64 (0.50-0.82),
p=0.0004
39%
RRR
47%
RRR

2019年
*Nominally significant, prespecified exploratory outcome; Renal composite outcome: sustained ≥40% eGFR decline to <60 mL/min/1.73 m2, ESKD, or renal death
N Engl J Med. 2019 Jan 24;380(4):347-357.
基層常見的患者，多半未發生過心血管事件，
這些患者使用 SGLT2i可否提供腎臟保護呢？
45%
RRR
eCVD
HR 0.55
(95%CI 0.41-
0.75)
49%
RRR
MRF
HR 0.51
(95%CI 0.37-
0.69)
P
interaction= 0.72
DECLARE TIMI-58
其中高達 6 成患者未曾發生過心血管事件
僅具多重風險因子 (MRF)**
HR 0.53 (95%CI 0.43-0.66)
p<0.0001*
47%
RRR
多重風險因子 **
「不論有無發生過心血管事件」
T2D患者使用 Forxiga
Ⓡ
可有效下降 45-49%腎臟惡化風險
29
29

「不論T2D患者eGFR 及UACR 高低」
使用Forxiga
Ⓡ
皆可有效保護腎臟
Prespecified exploratory renal endpoint: decrease eGFR ≥40% to <60 mL/min/1.73 m2, ESRD or Renal Death; UACR = urine albumin-creatinine ratio.
Lancet Diabetes Endocrinol. 2019 Aug;7(8):606-617.
50%
46%
48%
41%
62%
45%
49%
40%
2019年
30
30

31
DAPA-CKD: All-cause mortality
N Engl J Med. 2020 Oct 8;383(15):1436-1446.
2152 2039 2029 2017 1998 1925 1531 1028 398
2152 2035 2018 1993 1972 1902 1502 1009 379
DAPA 10 mg
Placebo
DAPA 10 mg
101 events
Placebo
146 events
0
2
4
6
8
10
12
0 4 8 12 16 20 24 28 32
Months from Randomization
Cumulative Incidence %
N at Risk
HR (95% CI) p-value
0.69 (0.53-0.88)0.0035
31%
RRR

不同原因之 CKD患者
使用Forxiga
Ⓡ
一致延緩腎功能惡化
WheelerDC. Presented at: ASN –Kidney Week 2020; October 22 –October25, 2020.
2020年
32
32

Ref. 105 年高屏區大內科 (內、家醫、小兒、腎內科 )審查醫師研討會議紀錄
Ref. 109 年高屏區大內科審查醫師研討會會議紀錄
洗腎免停可繼續使用
33

Case sharing
34

TW-23170 _FOR_14/02/2023
35
Case 1baseline characteristics
吳先生
58歲服務業
T2DM duration (14 year)
Biometric
HbA1c (%) 10.6
eGFR (ml/min/1.73m
2
) 115.3
UACR (mg/g) (UPCR) 52.4
Serum Creatinine (mg/dl) 0.75
BP (mm Hg) 116/82
LDL (mg/dL) 152
Uric acid (mg/dL) 5.6
History
Hypertension
Dyslipidemia V
Smoking
Hyperthyroidism V
MI
Gout
Others…
最
近
一
次
就
診
發
現
症狀描述 :
容易累、四肢麻痛、出現泡泡尿等 …….

TW-23170 _FOR_14/02/2023
Persistent albuminuria categories
Description and range
A1 A2 A3
<30 mg/g
<3 mg/mmol
30-300 mg/g
3-30 mg/mmol
>300 mg/g
>30 mg/mmol
GFR categories
(ml/min per 1.73m
2
)
Description and range
G1 ≥90
G2 60-90
G3a 45-59
G3b 30-44
G4 15-29
G5 <15
36
Reference: N EnglJ Med . 2019 Jan 24;380(4):347-357.; Kidney Int . 2020 Oct;98(4S):S1-S115
吳先生
58歲服務業
T2DM duration (14 year)
Green, low risk (if no other markers of kidney disease, no CKD); yellow, moderately increased risk; orange,
high risk; red, very high risk.
CKD風險分期情況
CKD

TW-23170 _FOR_14/02/2023
37
治療經驗分享
Anti-diabetic Medication
Metformin 500mg BID
Amepiride2mg QN
Other Medication
Nil
目前用藥
本次藥物調整的治療目標
降低蛋白尿、穩定血糖、減
少腎病變風險

TW-23170 _FOR_14/02/2023
38
治療經驗分享
Anti-diabetic Medication
Metformin 500mg BID
Amepiride2mg QN
Crestor 10mg QD
Other Medication
Methimazole 5mg 1# qd
目前用藥調整用藥
Anti-diabetic Medication
Metformin 500mg BID
Amepiride1mg QN
FORXIGA 5mg QD
CRESTOR 10MG QD
Other Medication
Methimazole 5mg 0.5# qd

TW-23170 _FOR_14/02/2023
Case1:a few years later…
Anti-diabetic Medication
Metformin 500mg BID
FORXIGA 10mgQD
ONGLYZA
Amepiride 1mg QN
TZD
GLP-1RA
Insulin
10.6
7.5
7.9
8.1
7.8
8.68.6
7.67.6
7.1
8.2
7.9
8.4
7.8
8.3
7.87.7
5
6
7
8
9
10
11
HbA1c (%)
39

TW-23170 _FOR_14/02/2023
Case1: a few years later…
52.4
36.5
42.5
2120.6
36.8
25
12.9
11.7
18.7
8.2
24.6
0
10
20
30
40
50
60
UACR (mg/g)
115.3
96.8
113.2
116.7
105.2
100.5
122
111.1
148.1
106.3
125.6
90.1
110.7
100.1
104104
117.3
0
20
40
60
80
100
120
140
160
eGFR (ml/min/1.73m
2
)
40

TW-23170 _FOR_14/02/2023
41
Case2 baseline characteristics
洪先生
82歲退休
T2DM duration (41 year)
Biometric
HbA1c (%) 8.7
eGFR (ml/min/1.73m
2
) 45.2
UACR (mg/g) (UPCR) 338.1
Serum Creatinine (mg/dl) 1.83
BP (mm Hg) 159/69
LDL (mg/dL) 182
Uric acid (mg/dL) 3.9
History
Hypertension V
Dyslipidemia V
Smoking
HF
MI
Gout
Others…
最
近
一
次
就
診
發
現
症狀描述 :
容易累、頻尿夜尿 , 血壓異常過高、
出現泡泡尿等 …….

TW-23170 _FOR_14/02/2023
Persistent albuminuria categories
Description and range
A1 A2 A3
<30 mg/g
<3 mg/mmol
30-300 mg/g
3-30 mg/mmol
>300 mg/g
>30 mg/mmol
GFR categories
(ml/min per 1.73m
2
)
Description and range
G1 ≥90
G2 60-90
G3a 45-59
G3b 30-44
G4 15-29
G5 <15
42
Reference: N EnglJ Med . 2019 Jan 24;380(4):347-357.; Kidney Int . 2020 Oct;98(4S):S1-S115
洪先生
82歲
T2DM duration (41 year)
Green, low risk (if no other markers of kidney disease, no CKD); yellow, moderately increased risk; orange,
high risk; red, very high risk.
CKD風險分期情況
CKD

TW-23170 _FOR_14/02/2023
43
治療經驗分享
Anti-diabetic Medication
Metformin 500mg TID
DiaminMR 30mg QDA
Glitos15mg QN
Other Medication
Exforge5/80 QN
Crestor 10mg QN
目前用藥
本次藥物調整的治療目標
降低蛋白尿、減少腎病變風
險、預防洗腎

TW-23170 _FOR_14/02/2023
44
如何幫助患者達到優質 DKD照護指標，
治療經驗分享
Anti-diabetic Medication
Metformin 500mg TID
DiaminMR 30mg QDA
Glitos15mg QN
Other Medication
Exforge5/80 QN
Crestor 10mg QN
目前用藥調整用藥
Anti-diabetic Medication
Metformin 500mg TID
DiaminMR 30mg QD
FORXIGA 10mg QD
Other Medication
Exforge5/80 QD
Crestor 10mg QN

TW-23170 _FOR_14/02/2023
Case 2:
Anti-diabetic Medication
Metformin 500mg BID
FORXIGA 10mg QD
ONGLYZA
DiaminMR 30mg QD
TZD
GLP-1RA
Insulin
8.7
7.1
6.8
7.2
6.9
6.7
7.57.5
7.1
7.4
7.5
7.17.1
7.47.4
5
5.5
6
6.5
7
7.5
8
8.5
9
HbA1c (%)
45

TW-23170 _FOR_14/02/2023
Case 2
338.1
7.19.4
118.3
26.3
15.1
24.921.215.7
24.1 21.9
0
50
100
150
200
250
300
350
400
UACR (mg/g)
45.245.9
44.8
4847.8
45.5
47.8
49
46.846.647.2
49.2
4544.1
42
0
10
20
30
40
50
60
70
80
90 eGFR (ml/min/1.73m
2
)
46

TW-23170 _FOR_14/02/2023
47
Case3 baseline characteristics
周女士
79歲燒肉飯
Biometric
HbA1c (%) 5.3
eGFR (ml/min/1.73m
2
) 62.7
UPCR (mg/g) 520.7
Serum Creatinine (mg/dl) 0.92
BP (mm Hg) 127/78
LDL (mg/dL) 137
Uric acid (mg/dL) 5.1
History
Hypertension V
Dyslipidemia V
CHF class II V
Af V
DM
Gout
Others…
最
近
一
次
就
診
發
現
症狀描述 :
容易喘容易累、頻尿夜尿 , 血壓異常過
高、出現泡泡尿、下肢水腫等 …….

TW-23170 _FOR_14/02/2023
Persistent albuminuria categories
Description and range
A1 A2 A3
<30 mg/g
<3 mg/mmol
30-300 mg/g
3-30 mg/mmol
>300 mg/g
>30 mg/mmol
GFR categories
(ml/min per 1.73m
2
)
Description and range
G1 ≥90
G2 60-90
G3a 45-59
G3b 30-44
G4 15-29
G5 <15
48
Reference: N EnglJ Med . 2019 Jan 24;380(4):347-357.; Kidney Int . 2020 Oct;98(4S):S1-S115
周女士
79歲
Green, low risk (if no other markers of kidney disease, no CKD); yellow, moderately increased risk; orange,
high risk; red, very high risk.
CKD風險分期情況
CKD

TW-23170 _FOR_14/02/2023
49
治療經驗分享
CO-MIDIS 80/5mg QD
Aldactone 25mg QD
Crestor 10mg QN
Pradaxa 110mg 1# BID
Nebilet5mg QD
目前用藥
本次藥物調整的治療目標
降低蛋白尿、減少腎病變風
險、改善心衰竭症狀

TW-23170 _FOR_14/02/2023
50
如何幫助患者達到優質 CKD照護指標，
治療經驗分享
CO-MIDIS 80/5mg QD
Aldactone 25mg QD
Crestor 10mg QN
Pradaxa 110mg 1# BID
Nebilet5mg QD
目前用藥調整用藥
CO-MIDIS 80/5mg QD
Aldactone 25mg QD
Crestor 10mg QN
Pradaxa 110mg 1# BID
Nebilet5mg QD
FORXIGA 10mg QD

TW-23170 _FOR_14/02/2023
Case 3: a few months later…
520.7
482.1
243.9
0
100
200
300
400
500
600
2023/3/92023/9/212024/3/62024/6/6
UPCR (mg/g)
62.7
57
61.8
65.9
0
10
20
30
40
50
60
70
80
90
2023/3/92023/3/212024/3/62024/6/6
eGFR (ml/min/1.73m
2
)
51

TW-23170 _FOR_14/02/2023
•CASE 1:DKD STAGE 1 WITH ONLY MICROALBUMINURIA
•CASE 2:DKD STAGE 3a-b AND PROTEINURIA
•CASE 3:CHF NYFC II AND CKD STAGE 2 -3a PROTEINURIA
52
CONCLUSION

53
1.all-cause mortality HR=0.69 (95%CI 0.53-0.88), p=0.0035 2. all-cause mortality HR=0.83 (95%CI 0.71-0.97), p=0.0217; 3. all-cause mortality HR=0.90 (95%CI 0.82-0.99), p=0.03
舊版：
用於心衰竭(NYHA分類第二至四級 ) 且心室射出分率降低 (≤ 40%)的成人時，可降低心血管死亡和
心衰竭住院的風險。
1.移除LVEF≤ 40%限制
2.新增”心衰竭緊急就醫 ”
2023/8/15 放寬心衰竭核准族群
預防DKD、心衰竭住院
治療心衰腎衰，顯著降死亡
FORXIGA唯一SGLT2i
治療T2D
預防DKD、hHF
治療HF，顯著降死亡
2,3
治療CKD，顯著降死亡
1
2023/8/15 放寬心衰竭核准族群

54
1.eGFR低於45的第二型糖尿病病人使用 Forxiga可預防心血管事件及預防腎臟病，不建議血糖控制 2.不建議開始治療，然而 Forxiga治療後， eGFR降低小於25的病人，可持續使用以降低 eGFR下降、ESKD、心血管死亡和心衰竭住院的風險。
3.對於eGFR低於30 的第二型糖尿病成人病人，不建議使用 Empagliflozin改善其血糖控制。根據其作用機制， Empagliflozin在此情況下可能無療效 . 4.若eGFR 低於30 ，則empagliflozin 建議劑量限於 10 mg;
參考資料:衛福部食藥署仿單 (更新至2024.5.24) 5.請勿對該病人新處方本藥
SGLT2i臺灣核准 eGFR劑量用法(2024.5.24)
eGFR 25
Empagliflozin 10 mg
糖尿病
心衰竭
eGFR 30
Empagliflozin 25 mg
腎臟病開始使用持續使用，洗腎免停
2
心衰竭開始使用持續使用，洗腎免停
2
開始使用
糖尿病
eGFR 30
開始使用
Canagliflozin糖尿病
eGFR 30
開始使用
eGFR 45
開始使用糖尿病持續使用，洗腎免停
2控糖+
心腎保護
心腎保護
1
開始使用
ESRD
續用
腎臟病開始使用
心腎保護使用時劑量不可提升
3,4
✓
✓
✓
✓
χ審慎評估是否繼續給藥
5
eGFR 30
eGFR 30
使用時劑量不可提升
4
✓
✓
FORXIGA唯一SGLT2i
糖心腎治療同劑量
及時開始預防 , 一錠守護到底
使用時劑量不可提升
4
不建議使用 ✓

55
LDL膽固醇也很重要

2022 台灣血脂治療指引建議初級預防患者
(如:糖尿病、CKD) LDL-C < 100mg/dL
56

USFDA Website: CRESTOR 10mg/20mg 可降低47%/55%
LDL-C
57
% ↓ LDL-
C
AtorvastatinFluvastatinPitavastatinLovastatinPravastatin
Ezetimibe/
Simvastatin
Simvastatin
30% 40 mg 1 mg 20 mg 20 mg 10 mg
38% 10 mg 80 mg 2 mg 40/80 mg 40 mg 20 mg
41% 5 mg 20 mg 4 mg 80 mg 80 mg 10/10 mg 40 mg
47% 10 mg 40 mg 10/20 mg 80 mg
55% 20 mg 80 mg 10/40 mg
63% 40 mg 10/80 mg
* Based on individual statin efficacy data, not head to head comparisons between statins.
•Adapted from FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin)toreduce the risk of muscle injury. U.S. Food and Drug Administration.
Updated 2016. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm Last accessed: 19.12.2016.
•Rosuvastatin 40 mg is not indicated in Taiwan
FDA: Relative LDL-lowering Efficacy of Statin and Statin-based Therapies
*
1.http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm#aihp

TW-23170 _FOR_14/02/2023
58
THANK YOU FOR
YOUR ATTENTION
特別感謝元成診所陳登旺院長
投影片分享

1.用於具第二型糖尿病且已有心血管疾病 (CVD)或多重心血管風險因子的成人病人時， Forxiga可降低心衰竭住院的風險。
2.用於具第二型糖尿病且已有心血管疾病的成人病人時， Empagliflozin可降低心血管原因死亡的風險。
3.心衰竭成人病人
4*.紐約心臟學會 (NYHA)第二級至第四級的心臟衰竭成年病人 ;
5.針對第2型糖尿病患者，降低慢性腎臟病 (CKD)新發生或惡化的風險
臺灣SGLT2i核准適應症 FORXIGA
5, 10 mg
Empagliflozin 10
mg
Empagliflozin 25
mg
Canagliflozin
100 mg
Ertugliflozin
(台灣僅有複方 )
第2型
糖尿病
血糖控制有有有有有
預防心血管事件有
1
有
2
有
2
降低多重心血管風
險因子患者心衰竭
住院風險
有
1
預防新發腎臟病
5 有
5
治療慢性腎臟病
有有
有
糖尿病腎病變
(巨量蛋白尿期 )
治療心衰竭
有
3
(rEF, pEF,impEF)
有*
4
(NYHA II-IV rEF,
pEF)
預防DKD且治療CKD&HF
延緩洗腎無蛋白尿限制
T2DM: 第二型糖尿病 CVD: 心血管疾病 ; eGFR低於45的第二型糖尿病病人使用 Forxiga可預防心血管事件及預防腎臟病，不建議血糖控制 ; eGFR低於30
的第二型糖尿病病人不建議使用 Jardiance 改善血糖控制 ; 參考資料 https://info.fda.gov.tw/MLMS/H0001.aspx(更新至2024.4.2)
FORXIGA唯一SGLT2i
59

2024
依據指引進行照護
並使用具有心腎好處實 ?WB?
Re-assessment
regularly
60
60

現今臺灣平均每 8人中就有 1位患有CKD
但九成患者尚處於 Early Stage
CKD 盛行率11.9%
280萬
其中近
90%
為早期CKD患者
(Stage 1~3a)
為CKD患者
Wen CP, Cheng TY, Tsai MK, et al. Lancet. 2008;371(9631):2173-2182. doi:10.1016/S0140-6736(08)60952-6
61

定期篩檢eGFR及蛋白尿
並利用CKD風險分級來評估病人的檢驗頻率與預後狀況
Diabetes Care. 2022 Oct 3;dci220027.doi: 10.2337/dci22-0027.
DAROC Clinical Practice Guidelines for Type 2 Diabetes Care-2022, Taiwan, Diabetes Association of the R.O.C., 2022.
DM: diabetes mellitus, HF: heart failure Circulation. 2016 Aug 9;134(6):435-7.
CKD分類根據 :
▪病因
▪GFR (G)
▪白蛋白尿 (A)
白蛋白尿(mg/g)
A1 A2 A3
正常至輕度上升中度上升重度上升
<30 30-299 ≥300
腎絲球過濾率
GFR
(mL/min/1.73 m
2
)
G1 正常至高 ≥90
篩檢
1
治療
1
治療及轉介
3
G2 輕度下降 60-89
篩檢
1
治療
1
治療及轉介
3
G3a 輕度至中度下降 45-59
治療
1
治療
2
治療及轉介
3
G3b 中度至重度下降 30-44
治療
2
治療及轉介
3
治療及轉介
3
G4 重度下降 15-29
治療及轉介
3
治療及轉介
3
治療及轉介
4+
G5 腎衰竭 <15
治療及轉介
4+
治療及轉介
4+
治療及轉介
4+
Worse eGFR and albuminuria
links to higher incidence of heart failure
eGFR + UACR/PCR
62

DM, Early CKD 「DKD照護整合方案」
整理111年3月1日公告實施之支付標準第八章第二章
增進定期篩檢率落實指引遵囑度
提升DKD照護網
涵蓋率
第八部第二章
糖尿病及初期慢性腎臟病照護整合方案
健保署新增「糖尿病及初期慢性腎臟病照護整合
方案」簡化糖尿病腎病變整合照護流程、及早阻
緩末期腎病變發生
民國111年3月1日正式施行糖尿病及初期慢性腎臟病照護整合方案
(1110215公告，1121113更新)
糖尿病及初期慢性腎臟
病照護整合方案公告

糖尿病及初期慢性腎臟病照護整合方案新制
各P碼收案參考
P1407 P1408 P1408 P1409
(1) 糖尿病
DM
P4301 P4302 P4302
(2) 初期慢性腎臟病
Early CKD
(3) 糖尿病合併初期
慢性腎臟病
DM & Early CKD
P7001 P7001 P7002
7週以上 10週以上 10週以上
77天以上 161天以上
10週以上
10週以上
內容整理 111年3月1日公告實施之支付標準第八章第二章

糖尿病合併初期慢性腎臟病照護整合方案管理點數增加
收案
類型
(1) 糖尿病
DM
(2) 初期慢性腎臟病
Early CKD
(3) 糖尿病合併初期慢性腎臟
病
DM & Early CKD
收案
類型
(1) 糖尿病
DM
(2) 初期慢性腎臟病
Early CKD
(3) 糖尿病合併初期慢性腎臟
病
DM & Early CKD
適用情況 DM收案，CKD未
收案
CKD收案，DM未收
案
DM收案+CKD收案
收案
條件
最近九十天曾在該院
所診斷為糖尿病，至
少同院所就醫達二次
（含）以上者，才可
收案
慢性腎臟疾病 : CKD
Stage 1、2、期病人，
經尿液、血液檢查達到
備註條件。
於同院所同時由前開糖尿病及初
期慢性腎臟病收案之病人，於同
一次就診完成 DM & Early CKD
追蹤管理照護。
年度追蹤管理
點數估計
ａ
(單位: 每個案)
P1408C+P1409
C
1,400點
b
P4302C
800點
P7001C*3+P7002C
2000點
內容整理 111年3月1日公告實施之支付標準第八章第二章
備註: ａ.新收案點數未計入，每個案以年初收案完整追蹤至申報上限 b.以第一階段年度追蹤管理點數計算
NEW

eGFR、UACR列為整合照護定期追蹤必要項目
推動定期監測腎臟狀況之落實
66
收案
類型
(1) 糖尿病
DM
(2) 初期慢性腎臟病
Early CKD
(3) 糖尿病合併初期慢性腎臟
病
DM & Early CKD
年度追蹤管理 P1408C P4302C P7001C
項目
Blood檢驗
HbA1c、Glucose(AC)
、
醣化白蛋白
1
Serum Creatinin、LDL 、
HbA1c
2
HbA1c、Glucose(AC)、醣化白蛋白
1
、LDL、Creatinine
Urine檢驗 x eGFR、UPCR Urine Routine、eGFR、UACR
血壓 V V
CKD stage/抽菸 x V V
單次追蹤管理點數 200點 200點 400點
次數* 3 2 3
內容整理 111年3月1日公告實施之支付標準第八章第二章
1.醣化白蛋白 :無HbA1C檢驗者必填 ;2.DM必要
*假設前一年已收案者，年度最多申請次數
NEW

Renal outcome trial of SGLT-2i
67 1. N Engl J Med. 2019 Jun 13;380(24):2295-2306. 2. N Engl J Med. 2020 Oct 8;383(15):1436-1446. 3. N Engl J Med 2023; 388:117-127
Canagliflozin 100 mg Dapagliflozin 10 mg Empagliflozin 10 mg
Study CREDENCE DAPA-CKD EMPA-KIDNEY
Publish date April 14, 2019 (NEJM) Sep. 24, 2020 (NEJM) Jan. 12, 2023 (NEJM)
Status
stopped early on
demonstration of efficacy
stopped early for
overwhelming efficacy
stopped early due to evidence of efficacy
N 4402 4304 6609
Medium duration 2.6 years 2.4 years ~3.1 years
Patient population T2D
with or without T2D
(excluded T1D)
with or without T2D
(excluded T1D)
Renal population
inclusion criteria
eGFR ≥30 to <90mL/min/1.73 m
2
UACR >300 to ≤5000 mg/g
eGFR ≥25 to <75mL/min/1.73 m
2
UACR ≥200 and ≤5000 mg/g
eGFR ≥20 to <45 mL/min/1.73 m²
or
eGFR ≥45 to <90 mL/min/1.73 m²
with UACR ≥200 mg/g (or protein:creatinine
ratio ≥300 mg/g)
Primary Endpoint Doubling of serum creatinine, ESRD,
renal or CV death
≥50% sustained decline in eGFR,
ESRD, renal or CV death
1. ≥40% sustained decline in eGFR, ESRD,
sustained decline in eGFR to <10, renal
death
2. CV death

新陳代謝科
糖尿病治療新趨勢

What we meet in T2Dtreatment ?
DPP4i
SGLT2i
GLP-1RA
Beyond medication: how new technology to support DM patient
management(case sharing)
Outline

World
2045783 million
…↑
46%
Increase537 million2021
Western Pacific
2045260 million
…↑27%
Increase
3 million
206 million
2045
2021
Regional prevalence [20-79y]: 11.9%
Taiwan prevalence [20-79y]: 9.7%
Taiwan
↑…
50%
Increase2 million2021
Diabetes prevalence is increasingworldwide and in Taiwan

台灣糖尿病盛行率為 12.3%
社團法人中華民國糖尿病學會。 2022 第2 型糖尿病臨床照護指引。國家衛生院台灣糖尿病 2019年鑑
第2型糖尿病人數，節節上升
84.4
218.9 220.0
0
50
100
150
200
250
病人數（萬人）
2000 2014 2024
380萬人
以上
2.6X 1.7X
4.5X

Both YOUNGand OLD T2D patients are increasing in Taiwan
社團法人中華民國糖尿病學會。 2019老年糖尿病臨床照護手冊。
2.2 million
DM patients
>65yrs
50.3% (vs 30% globally)
♀56.4%♂44.6%
DM: diabetes mellitus; yrs: years.
In 2014
<40yrsnaïve pt’
160,000/Year
New diagnosed DM
patients
9,975
2000 2014
12,724
YoungT2D
OldT2D

Adopted from 台灣糖尿病年鑑 2019 第二型糖尿病
YODIncidence in Taiwan
<40yrsnaïve pt’

60%/8yrs

Characteristics of Taiwan YODpatients
Young Onset Diabetes Patient
2040
➔
years years
Longer Treatment Duration
Durability
Delay
Complications

Adopted from Nat RevEndocrinol volume 16 | June 2020
Young-onset type 2 diabetes mellitus
implications for morbidity andmortality

糖尿病越早發生壽命就越短
男性女性
【台灣糖尿病年鑑 2000-2009】
Journal of the Formosan Medical Association (2012) 111(11), 587-664
5-6 yrs 3-4yrs

Numberof people with diabetes in adults (20–79 years) by age group in 2021
and estimatedprevalenceacross age groups in 2045
https://diabetesatlas.org/idfawp/resource-files/2021/07/IDF_Atlas_10th_Edition_2021.pdf
>65yrs

糖尿病現況 100～109年主診斷為糖尿病人數 (年齡區分)
資料來源：健保署資料期間： 100.01~109.12/109.01~109.12資料條件：此處糖尿病定義為，主診斷碼符合國際分類第十版 ICD-10-CM 前三碼E08-E13
糖尿病專區 -Heho健康
https://heho.com.tw/diabetes
全國糖尿病人數
65歲以上

65 歲以上老年人的血糖控制目標
1. 社團法人中華民國糖尿病學會。第 2型糖尿病臨床照護指引。 2022年。Accessed on 19 June 2024.
正常
少共病症
認知及身體機能正常
空腹血糖
睡前血糖
HbA1c
血壓
健康狀態
80-130 mg/dL
80-180 mg/dL
<7-7.5 %
<140/90 mmHg
中等
多共病症，認知及身體機
能輕微至中等異常
90-150 mg/dL
100-180 mg/dL
<8.0 %
<140/90 mmHg
差
末期慢性病，認知及身體
機能中等至嚴重異常
100-180 mg/dL
110-200 mg/dL
不仰賴HbA1c 為目標，避免
產生低血糖或有症狀之高血糖
<150/90 mmHg
Framework for considering treatment goals for glycemia,
blood pressure, and dyslipidemia inolder adults with diabetes

Vascular Complications ofDiabetes
1
Vascular Complications Prevalence Characteristics Gender differences
Coronary heart disease14%-21%
Most frequently reported form of CVD
and most lethal one
Risk of death from CHD is higher in women then in
men (HR, 95% CI:1.81 [1.27-2.59] versus
1.48[1.10-1.99])
Heart failure 19%-26%
Second most common initial manifestation
of CVD in T2DM
Risk of HF is up to 2-fold in men and 5-fold
in women
Peripheral artery disease16%-29%
Most common initial manifestation
of CVD in T2DM
Prevalence is 1.8-fold higher in women
compared to men
Stroke 8%-12%
Second more frequent cause of death in patients
with T2DMafter CHD
Prevalence is similar in men and women
Retinopathy 34%
Most common microvascular complication
of diabetes; responsible of 2.6% of all cases of
blindness worldwide
Prevalence rates are higher in T1DMcompared to
T2DM(77.3 vs. 25.2%).
-
Neuropathy 31%-73% Cardiac autonomic neuropathy
No difference in prevalence between men
and women
Nephropathy 29%-61%
Leading cause of end stage renal disease
in the adult population worldwide
Female sex is a risk factor for nephropathy
in T2DM
CHD, coronary heart disease; CI, confidence interval; CVD, cardiovascular disease;HF, heart failure; HR, hazard ratio;T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus.
1. Dal C antoE, et al. EurJ PrevCardiol. 2019;26(2_suppl):25-32.
The prevalence of DM complication

Despite availability of numerous treatments diabetes remains
a challenge
Zheng Y et al. Nature Rev Endocrinol 2018;14:88–98.
25%
of T2D patients have
diabetic kidney disease
27%
present with microvascular
complications
Diabetes remains the 9
th
major cause of death
globally
50%
of patients with T2D present
with macrovascular
complications

Improving GlycaemicControl ReducesRisks of Long-term Complications
The decrease in risk of long-term diabetes complications for each 1 %reduction in updated mean HbA
1C
43% 37% 19% 16% 14% 12%
Stroke
Myocardial
infarction
Heart
failure
Cataract
extraction
Microvascular
disease
Lower extremity
amputation or fatal
peripheral vascular
disease
1. Stratton IM, et al. BMJ. 2000;321(7258):405-12.

HbA
1Cachievement rate has improved over the years but is still
suboptimalin Taiwan
TADE 2002/2006/2011/2018 Survey
21.1
43.5
32.3
21.7
34.5
16.6
44.1
10.8
0
5
10
15
20
25
30
35
40
45
50
55
60
HbA
1C <7% HbA
1C ≥9%
2002
2006
200620112018
2X
4X

2024 ADA 病患若合併 ASCVD，HF，CKD時
指引中列為優先考量用藥的選擇
+ASCVD/
Indicators of
high risk
+HF +CKD
Either/or
SGLT2i
GLP-1RA
SGLT2i
SGLT2i
GLP-1RA

若病患沒有合併上述共病，指引中考量到不會低血糖與
不增加體重的藥物
Compelling need to
minimize hypoglycemia
Compelling need to
minimize weight gain or
promote weight loss
Cost is a major
issue
SGLT2i GLP1-RA
TZDDPP4i
or
SGLT2i
or
GLP1-RA
SU
or
TZD
If A1C above individualized target proceed as below
Without established ASCVD, CKD, HF

指引中依據降血糖效力分級
血糖控制 :選擇能提供療效以達成目標的方法
Metformin或包含合併療法在內的藥品 (們)，
能提供足夠療效來達成且維持治療目標
在高風險族群，優先考慮避免低血糖的發生
一般來說，具有更高療效的方法有更高的機率達成血
糖目標
降血糖效力 :
非常高:
Dulaglutide (high dose),
Semaglutide, Tirzepatide
Insulin
Combination Oral, Combination Injectable (BLP-1 RA/Insulin)
高:
GLP-1 RA (not listed above), Metformin,
SGLT2i, Sulfonylurea, TZD
中等:
DPP-4i
指引中依據降體重療效將藥品分級
達成及維持體重控制目標
設定個人體重控制目標
一般生活方式建議 :
醫學營養治療 /飲食習慣 /
體能活動
考慮以藥物進行減重
密集的具實證架構之
體重管理計畫
考慮代謝性手術
當選擇降血糖療法時 :
考慮同時在血糖及體重都具有高到非常高效力的療程
降體重效力
非常高:
Semaglutide, Tirzepatide
高:
Dulaglutide, Liraglutide
中等:
GLP-1 RA (not listed above), SGLT2i
中性:
DPP-4i, Metformin

22
HFrEF HFpEF
ESC recommend SGLT2inhibitorsas
first-line HFrEFtherapy*
1
SGLT2inhibitors are recommended as
foundational therapy for patients with
HF
1–3
“SGLT2ishould be initiated in
all HFpEFpatients
without contraindications”
2023 AHA/ACC/HFSAGuidelines
3
2021 ESC Guidelines
1
2021 CCS/CHFS Guidelines
2
2022 AHA/ACC/HFSA Guidelines
3
Guidelinesrecommend SGLT2inhibitors for people with HF
Guidelines recommend the use of SGLT2inhibitorsacross the CV, renal and metabolicspectrum
2023 AHA/ACC/HFSA

2024KDIGO針對糖尿病合併 CKD治療指引

PC-TW-105332-
20230609
2023 ESC Guidelines for the management of CVD in patients with DM

195019601970198019902000201020122013
A closer look at CV effects of 21st century T2D agents
CV, cardiovascular; DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1; SGLT2, sodium-glucose co-transporter-2; SU,
sulphonylurea; T2D, type 2 diabetes; TZD, thiazolidinedione
Adapted from: Kirby MG. Br J Diabetes Vasc Dis2012;12:315; 1. Sanofi US. Lantus
®
(insulin glargine injection) USPI, 2015
Lente class
of insulins
produced
SUs first
used
Recombinant
human insulin
produced
2nd
generation
SUs available
Three new classes introduced:
-glucosidase inhibitors,
meglitinides and TZDs
Glimepiride: 3rd
generation SU
DPP-4
inhibitors
GLP-1 receptor
agonists
SGLT2
inhibitors
Insulin
degludec
Older T2D agents
Insulin glargine
available
1
Metformin
introduced
in the UK
Newer T2D agents →
DPP-4 inhibitorSGLT2 inhibitor GLP-1 receptor agonist Other

What we meet in T2Dtreatment
DPP4i
SGLT2i
GLP-1RA
Beyond medication: how new technology to support DM patient
management(case sharing)
Outline

Limitations of AntihyperglycemicDrugs in Renal impairment pt’
Metformin
Insulin
SU TZD
DPP4i
SGLT2i
GLP1
Edema、HF
Lactic
acidosis
Decrease of
Efficacy
Increase risk of
Hypoglycemia
2020/5/1
Reimbursement
Restriction
健保給付規範第五節激素及影響內分泌機轉藥物

Efficacy of SGLT2i is highly associated with kidney function
Adv Ther. 2017 Nov 28. doi: 10.1007/s12325-017-0639-z
When eGFR Decline
•Efficacy of HbA1c
•Efficacy of Fluctuation
5X

Y. G. Kim et al. Diabetologia(2013) 56:696–708
•DPP4is shows significant efficacy across all BMI and
Ethnicity subgroups
Especially in Asianand BMI 24-26.
DPP4iis more effective in Asians and Lean Diabetes

Japan Oral antidiabetic drug (OAD) prescribing patterns in patients with
type 2 diabetes by year from 2002 to 2019
J Diabetes InvestigVol. 13 No. 1 January2022
DPP4i

Prandialglucose contributed more when HbA1c < 8.5%
International Journal of Endocrinology Volume 2019, Article ID 1267475, 5 pages
< 7.1 % 7.1-7.5% 7.6-8.0% 8.1-8.7% 8.8-12.7%

Using the respective contributions of postprandial fortailoring
treatments
Diabetes & Metabolism41 (2015) 179–182

Special considerations in the management of type 2 DM
in Taiwan
Durability
&
Persistence
Sacropenia
&
T2DM
Glycemic
Variability
&
Hypoglycaemia

Durability
&
Persistence
34

Decline of Beta Cell Function is critical issue to T2D Patients
35
Yoshifumi Saisho; J. Clin. Med. 2014, 3, 923-943
Time

Different glucose-lowering agents impacts to
beta cell function
1.Yoshifumi Saisho. EXPERT OPINION ON PHARMACOTHERAPY.2020
An emerging new concept for the management of type 2 diabetes with a paradigm shift from the glucose-centric to beta cell-centric concept of diabetes -an Asian perspective
2.Del Prato S, CamisascaR, Wilson C, et al. Diabetes Obesity Metab. 2014;16(12):1239–1246.
Durability of the efficacy and safety of alogliptincompared with glipizide in type 2 diabetes mellitus: a 2-year study.
Beta cell
protective
Effect
Restore islet
function
Metformin Yes -
DPP4i Yes
GLP-1RA Yes
SGLT2i Yes -
α-glucosidase
inhibitor
Yes -
TZD Yes -
SU No
Glinide No
insulin Yes -
DPP4i is the only oral medication that
can RESTOREBeta Cell function

DPP4i has lowest risk of side effect, which can improve patient adherence
2020台灣糖尿病治療指引
安全性佳,低血糖風險低 ,
不增加體重

DPP4idemonstrate the best 36 months durability in
DISCOVER study
Kamlesh Khuntiet al. Diabetes Obesity and Metabolism. 2021 Apr.
https://publons.com/publon/10.1111/dom.14400.
*Denotes statistically significant differences (P < 0.05).
38 Countries
Age ≥ 18
7613 patients
(18.5% Asian)
DISCOVER Study
Benefit of 2
nd
Line
Medication
3 Year Follow-up
36 month

DPP-4 inhibitors demonstrate best persistence and adherencein
real-world patients
Nishimura R, et al. BMJ Open. 2019;9(3):e025806.
Persistence with monotherapyschedules of index antidiabetic drug classes
α-GI: α-glucosidase inhibitor; BG: biguanide; DPP-4i: dipeptidyl peptidase-4 inhibitors; JMDC, Japan Medical Data Center; MDV: Medical Data Vision;pts: patients; SGLT-2i: sodium-glucose cotransporter-2 inhibitor; SU: sulfonylurea; TZD: thiazolidinedione; UT: untreated.
1138
582
384
280
400
161
471
0
200
400
600
800
1,000
1,200
SGLT-2i
Median time to
discontinuation (days)
BGDPP-4i SU α-GI GlinideTZD
JMDC database, N= 40908
Adapted from table 2. Nishimura R, et al. BMJ Open. 2019;9(3):e025806.

Sacropenia
&
T2DM
40

Muscle strength and the life course
Age and Ageing 2019; 48: 16 –31
20-30 肌少症

Risk Factors of Sarcopenia
•Mechanism of each medication
•Number of Chronic Disease
1.YaSuet al. J Clin Med. 2019 Mar; 8(3): 291.
2.Noriko Ogamaet al. J Clin Med. 2019 Mar 6;8(3):319
DiabetesPolypharmacy
•Hyperglycemia
•High Glucose Fluctuation
2
Age Low BMI

Prevalence of OLD T2Dpatients in Taiwan is higher than in global
average
43
社團法人中華民國糖尿病學會。 2019老年糖尿病臨床照護手冊。
2.2 million
DM patients
>65yrs
50.3%
♀56.4%♂44.6%
DM: diabetes mellitus; yrs: years.
In 2014

Asian T2D patients typically have a lower BMI
*Bangladesh, China, Hong Kong, India, Indonesia, Korea, Pakistan, Singapore, Taiwan, Thailand, and Vietnam.
1. Freemantle N, et al. Diabetes ObesMetab. 2012;14(10):901-909. 2. Tsai S, et al. J Diabetes.2011;3(3):208-216. 3. Kim S, et al. ActaDiabetol. 2014;51(4):655-661.
BMI
35
30
25
20
15
10
5
0
32.4
30.7
31.5
Region
29.6
23.9
26.1
24.3
Canada
1
E. Europe
1
N. Europe
1
S. Europe
1
Japan
1
Asia*
2
Korea
3
BMI of T2DM patients in different area

Number of Chronic Disease is highly associated with
risk of Sarcopenia
Li et al. BMC Geriatrics (2015) 15:11
*
*TUG test: Timed Up and Go test

(eBook) https://doi.org/10.1007/978-981-10-4376-5
Accelerating risk factors for sarcopenia

Hyperglycemia Is Associated with Impaired Muscle Quality
in Older Men with Diabetes in Korea
The Korean Longitudinal Study on Health and Aging
(cross sectional design)
Diabetes MetabJ 2016;40:140-146
*Short Physical Performance Battery (SPPB) scores
(balance, walking and muscle strength)

Antidiabetic Agents in Sarcopenia-SU
1.Antonietta Mele et al. Pharmacol Res Perspect 2014 Feb;2(1):e00028. doi: 10.1002/prp2.28. Epub 2014 Mar 3
Sulfonylureas and glinidesinduced atrophy in skeletal muscle
*All Sulfonylureas decrease
skeletal muscle weight in
different muscle group
屈趾短肌 (flexor digitorum brevis, FDB)、比目魚肌
(soleus)、趾長伸肌 (extensor digitorum longus,EDL)

DPP-4i 優於SU 組可顯著增加骨骼肌重量與質量
•Body Composition and Sarcopenic Indices of the Study Participants, According to Antidiabetic
Therapy
FFM (kg)
FM (kg)
FFM/FM
FFM index (kg/m
2
)
SMM (kg)
SMM index (kg/m
2
)
Handgrip strength (kg)
Gait speed 4 m (m/s)*
51.8 ±7.1
19.7 ±1.6
2.6 ±0.4
19.1 ±2.2
22.4 ±5.3
8.2 ±1.7
23.5 ±4.9
3.5 ±0.7
49.4 ±6.5
19.9 ±1.7
2.5 ±0.3
18.4 ±2.1
20.5 ±4.7
7.6 ±1.5
21.4 ±4.2
3.7 ±0.7
.001
.186
.001
.001
.001
.001
.001
.001
54.5±6.8
19.4 ±1.6
2.8 ±0.4
19.9 ±2.1
24.7 ±5.3
9.0 ±1.6
26.1 ±4.4
3.1 ±0.6
不包含脂肪的重量
脂肪的重量
骨骼肌的重量
All
Patients
(N = 80)
Sulfonylureas
Group
(n = 43)
P
Value
DPP4-I
Group
(n = 37)
DPP4-I, dipeptidyl peptidase 4 inhibitors; FFM, fat-free mass; FM, fat mass; SMM, skeletal muscle mass.
Data are expressed as mean ±standard deviation.
*The unit used, meters/second (m/s), expresses the time taken to cover a 4-m distance (a fixed
distance, 4 m) in a time period (seconds), which varies from participant to participant
2016 J Am Med Dir Assoc 17 (10): 896

Antidiabetic Agents in Sarcopenia–SGLT2i
Megumi Yasuda et al. J Diabetes Investig. 2020 May;11(3):745-747
+Insulin injection
+Nutrition supply
-withdraw SGLT2i
Admission
(psoas muscle mass index)
Proteinolysis
Protein synthesis
Fracture Risk
SarcopeniaRisk

The potential mechanism of SGLT2iandDPP-4Ion bone metabolism.
Open Access Published:16 November 2019 volume11,pages7–14 (2020)

DPP-4icould be associated with a reduced risk of bone fractures
Diabetes Care.2011 Nov;34(11):2474-6.

Antidiabetic Agents in Sarcopenia-DPP4i
DPP4iattenuates the decline of skeletal muscle mass in patients with type 2 diabetes
RyotaroBouchiet al. Diabetes MetabRes Rev. 2018 Feb;34(2). doi: 10.1002/dmrr.2957. Epub2017 Nov 23.
✓

Wen CY, Lien AS, Jiang YD
J Diabetes Investig. 2022;13(6):944-946. doi:10.1111/jdi.13752
Effect of glucose-lowering medications onmuscle mass in
type 2 diabetes patients

Glycemic
Variability
&
Hypoglycaemia
55
What is Glycemic Variability ?

Glycemic variability in the development of cardiovascular complications
in diabetes
Diabetes Metabolism Res, Volume: 34, Issue: 8, First published: 20 July 2018, DOI: (10.1002/dmrr.3047)
How to Measure Glycemic Variability(GV)?Standard deviation (SD), coefficient of variation (CV), mean amplitude
of glycemic excursions (MAGE)

MAGE
MMSE
MAGE
MACE
MAGE
MAGE
CAD
CKD

J ASEAN Fed EndocrSoc.2021;36(2):167-171.

Number of hypoglycemic events as a function of
tertiles of glycemic variability
High
glycemic variability

Hypoglycaemia has a broad range of outcomes and effects
Hypoglycaemia
Hospitalisation
costs
4 Cardiovascular
complications
3
Weight gain by
defensive eating
5
Loss of
consciousness
3
Increased risk
of seizures
3
Increased risk
of car accident
6
Reduced
quality of life
7
Increased risk
of dementia
1
Death
2,3
Coma
3

A bidirectional interaction between hypoglycemia and dementia
Patients with hypoglycemia : +68% risk of dementia
Patients with dementia: +61% risk of hypoglycemia
•MattishentK1&Loke YK; Diabetes ObesMetab. 2016 Feb;18(2):135-41

1. Y.-H. Lin. Journal of Internal Medicine of Taiwan 29(2):86-91
糖尿病可能導致失智症的致病機轉分成五大類：
高血糖、低血糖與血糖波動
糖尿病與失智症

DPP-4i 相較於SU 在第二型糖尿病患
能改善老年人的認知功能分數 (MMSE)
25
25.5
26
26.5
27
27.5 MMSE
DPP-4 inhibitors Sulfonylureas
Glimepiride, glyburide, or glipizide (n = 120)
Vildagliptin, sitagliptin, saxagliptin(n = 120)
•DPP-4i baseline vs 2-year treatment:
p <0.05
•DPP-4i vs SU at 2-year treatment:
p <0.05
Drug-naive T2DM
Mild cognitive impairment
2014 J GerontolA Biol Sci Med Sci 69:1122

49%
26%

Conclusions(1)
•The AgingT2DMand YODpatient is a growing challenge for Taiwan
•DPP4iare safeand effectivein controlling the blood glucose in patients with
T2DM
•DPP4ishows positive safety profile in skeletal muscleand decreased the risk of
fracture in T2DM
•Early intensificationconcept has becomes important and should be implemented
–VERIFY is the first study to investigate the long-term clinical benefits of initial
combination treatment versus the standard-of-care MET monotherapy
–Early combination treatment showed improveβ-cell function and Prandial
insulin secretioncompared with initialmonotherapy.
DPP4i

•Glycemic variability is an important indicator for diabetes control and safety
–Vildagliptin provides better MAGEand TIRcontrol
•For elderlyDM patient
-Hypoglycemia should be avoided in older adults with diabetes.
-DPP4ishows lower rate of hypoglycemiaand did not affect cognitive
function.
-DPP4ishows well HbA1cand GV efficacy and safetyprofile in Elderly
•DPP4ishows well efficacy and tolerance for renal impairment DM patient.
Conclusions (2)
DPP4i

DPP4ieGFR (<45) limitation updates
(5mg)
(5mg)
(100mg)
(100mg) (25mg)
(50mg)
(2.5mg)
(50mg)

What we meet in T2Dtreatment
DPP4i
SGLT2i
GLP-1RA
Beyond medication: how new technology to support DM patient
management(case sharing)
Outline

International guidelines
recommend the use of
an SGLT2inhibitor such as
as early as first-linetherapy
2–5
HF
ASCVD T2D
CKD
ADA–EASD
3
ADA–KDIGO
4
ADA
5
KDIGO
6
ESC
7
AHA/ACC/HFSA
8
CCS/CHFS
9
PCDE
2
KDIGO
1
ADA–EASD
3
ADA
4
The interrelated cardio-renal-metabolic (CRM) systems

ADA和KDIGO針對糖尿病合併 CKD治療的新聯合聲明
降糖用藥建議

Forxiga® vs. Jardiance
®

T2Dpatients
StartForxiga®early to manage the CRM systems
PC-TW-105332-
20230609
SGLT-2 inhibitors are recommended by multiple practice guidelines globally,
including ADA, DAROC, ESC/EASD, KDIGO
1-4
HF patients
CKD patients
HF patients

糖尿病腎病變照護需要及早介入
120 150 150 90 60 <10GFR (ml/min)
Serum Creatinine (mg/dl)0.9 0.8 0.8 1.0 >2.0 >10
• UARC: urine albumin to creatinine ratio 1. DeFronzo, R. A. Diabetes Reviews, Vol. 3, No. 3, 01.01.1995, p. 510-564. 2. Sem Nephrol10:184-193, 1990.
• 3. Sci Rep. 2018 Mar 20;8(1):4909. 4.https://somepomed.org/articulos/contents/mobipreview.htm?36/63/378835. J Am SocNephrol.2017 Apr;28(4): 1023-1039.
“Silent Period”
-3 0 3 15 20 24TIME (years)
Onset of
Diabetes
Onset of
Diabetic
Glomerulosclerosis
Onset of
Albuminuria
ESRD
UACR (mg/g)0 0 10 >100 >300
Normoalbuminuric diabeticglomerular
<10years
>30
eGFR為升高或正常，但腎病變已發生(腎元可能已受損 50%)
10
糖尿病
診斷
微量蛋白尿巨量蛋白尿洗腎“Silent Period”
在T2DM中對於CVD的預測力強
eGFR快速下降，約十年內即進展至末期腎病。
但約20%患者遲至洗腎都不會出現蛋白尿
DeFronzo教授：應自 “Silent Period關鍵期”
介入糖尿病腎病變照護

120 150 150 90 60 <10GFR (ml/min)
Serum Creatinine (mg/dl)1.0 0.8 0.8 1.0 >2.0 >10
UARC: urine albumin to creatinine ratio 1. DeFronzo, R. A. Diabetes Reviews, Vol. 3, No. 3, 01.01.1995, p. 510-564.
2. Sem Nephrol10:184-193, 1990. 3. Sci Rep. 2018 Mar 20;8(1):4909. 4.
“Silent Period”
-3 0 3 15 20 24TIME (years)
Onset of
Diabetes
Onset of
Diabetic
Glomerulosclerosis
Onset of
Albuminuria
ESRD
UACR (mg/g)0 0 10 >100 >300
Normal glomerulus Diabetic nephropathy Advanced diabetic glomerulosclerosisNormoalbuminuric diabeticglomerular
9years
>30
收納9成eGFR≥60且近7成UACR<30 mg/g的T2D患者使用FORXIGA10 mg
DECLARE提供T2D患者silent period以FORXIGA治療實證

FORXIGA治療T2D病患
減少腎功能惡化、 ESRD或腎因性死亡
Acute kidney injury
針對9成eGFR≥60且近7成UACR<30 mg/g的T2D患者使用 FORXIGA10 mg
ESRD ↓ 69%
HR 0.31 (0.13-0.79),
p=0.013
47%
RRR
HR 0.53 (95%CI 0.43-0.66)
p<0.0001* 31%
RRR
HR 0.69 (95%CI 0.55-0.87)
p=0.002
Renal compositeoutcome*
*Nominally significant, prespecified exploratory outcome; Renal composite outcome: sustained ≥40% eGFR decline to <60mL/min/1.73 m2, ESRD, or renal death
1. N EnglJ Med. 2019 Jan 24;380(4):347-357. 2. Lancet Diabetes Endocrinol. 2019 Aug;7(8):606-617. 3. Diabetes ObesMetab. 2020 Aug;22(8):1357-1368.

Renal composite outcome: sustained ≥40% eGFR decline to <60 mL/min/1.73 m
2
, ESKD, or renal death
Diabetes Care. 2021 Aug;44(8):1805-1815.
FORXIGA 治療T2D患者無論白蛋白尿分級
一致減少腎臟惡化事件風險

DAPA-CKD提供FORXIGA治療白蛋白尿患者實證
120 150 150 90 60 <10GFR (ml/min)
Serum Creatinine (mg/dl)1.0 0.8 0.8 1.0 >2.0 >10
UARC: urine albumin to creatinine ratio 1. DeFronzo, R. A. Diabetes Reviews, Vol. 3, No. 3, 01.01.1995, p. 510-564.
2. Sem Nephrol10:184-193, 1990. 3. Sci Rep. 2018 Mar 20;8(1):4909.
“Silent Period”
-3 0 3 15 20 24TIME (years)
Onset of
Diabetes
Onset of
Diabetic
Glomerulosclerosis
Onset of
Albuminuria
ESRD
UACR (mg/g)0 0 10 >100 >300
Normal glomerulus Diabetic nephropathy Advanced diabetic glomerulosclerosisNormoalbuminuric diabeticglomerular
>30
有白蛋白尿病患使用 FORXIGA10 mg
9years

FORXIGA預防糖尿病腎病、治療 CKD
遠離洗腎、降低死亡
ACEI or ARBCKD患者
FORXIGA10 mg
Metformin糖尿病患者
預防CKD 治療CKD遠離洗腎
36%ESRD
69%ESRD
31%總死亡

DECLARE與DAPA-CKD合併分析
eGFR = estimated glomerular filtration rate; UACR = Urine Albumin-to-Creatinine Ratio
1. Moura F, et al. Presented at: ESC Congress 2022; August 26-29, 2022; Barcelona, Spain.
將DECLARE-TIMI 58 與DAPA-CKD 兩項試驗合併分析，心血管終點為心血管死亡或心衰竭住院，
腎臟終點為eGFR 持續減少 ≥ 40%、進展到末期腎病變、腎因性死亡。
按照eGFR 與UACR 之各組人數分布

DAPA-CKD&
DECLAREpooled
analysis:
FORXIGA於T2D
腎臟保護
不受eGFR及
蛋白尿多寡影響
https://esc365.escardio.org/presentation/251347

DAPAHF:FORXIGA針對EF≦40%的心衰竭試驗
Eur J Heart Fail. 2021 Jul;23(7):1217-1225.
Heart Failure with
Improved Ejection Fraction
HFimpEF
25 6030 35 45 5550
LVEF (%)
HFrEF HFmrEF HFpEF
Heart Failure with
Reduced Ejection Fraction
Heart Failure with
Mildly Reduced
Ejection Fraction
Heart Failure with
Preserved Ejection Fraction
Acute Phase
Discharge
Chronic Phase
In-hospital Outpatient
40

JAMA. 2020 Apr14;323(14):1353-1368.
Patients withoutT2D(n = 2605) Patients with T2D(n = 2139)
有/無糖尿病HF患者使用Dapagliflozin
皆能降低心衰竭惡化及心血管死亡
27%
RRR
25%
RRR

*nominal P value N EnglJ Med. 2019 Nov 21;381(21):1995-2008.
18%
RRR
CV Death All-cause Mortality
17%
RRR
Dapagliflozin唯一SGLT2i針對HFrEF
顯著減少心血管死亡、總死亡

FORXIGA10 mg
慢性收縮性
心衰竭患者
NYHAII-IV
LVEF≤40%
ACEI
or ARB
b-blocker
最大耐受劑量
≥4周
(初次使用需檢附
一年內指定檢查
之LVEF數值結果 )
ACEI
or ARB
因禁忌症而無法
使用b-blocker
≥4周
&
2021 ESC HF治療指引 class IA建議：
SGLT-2i為一線用藥，為HFrEF患者降低死亡
FORXIGA心衰竭健保給付流程
ESCHF指引建議一線降死亡藥物
FORXIGA心衰竭健保給付 2022年5月1日正式生效

DELIVER:FORXIGA針對EF>40%的心衰竭試驗
Eur J Heart Fail. 2021 Jul;23(7):1217-1225.
Heart Failure with
Improved Ejection Fraction
HFimpEF
25 6030 35 45 5550
LVEF (%)
HFrEF HFmrEF HFpEF
Heart Failure with
Reduced Ejection Fraction
Heart Failure with
Mildly Reduced
Ejection Fraction
Heart Failure with
Preserved Ejection Fraction
Acute Phase
Discharge
Chronic Phase
In-hospital Outpatient
40

DELIVER: Study Design
1. Solomon, S.D. et al. J Am Coll CardiolHF. 2022;10(3):184–197.2. Solomon SD et al. Online ahead of print. N EnglJ Med. 2022
318

Cumulative Incidence
(%)
1 2
Years sinceRandomization
Placebo
610events
9.6 (8.9-10.4) per100py
Dapagliflozin
512events
7.8 (7.2-8.5) per100py
HR 0.82, 95% CI0.73-0.92
P =0.0008
NNT =32
18RRR
%
3.1% ARR
p=0.0008
2
Primary Endpoint: CV Death or WorseningHF
FullPopulation

Componentsof PrimaryEndpoint
FullPopulation
Placebo
455events
7.2 (6.5-7.8) per100py
Dapagliflozin
368events
5.6 (5.1-6.2) per100py
HR 0.79, 95% CI0.69-0.91
P =0.001
0
5
10
15
20
25
Cumulative
Incidence
(%)
0 1 2
Years sinceRandomization
3
Placebo
261events
3.8 (3.3-4.3) per100py
Dapagliflozin
231events
3.3 (2.9-3.8) per100py
HR 0.88, 95% CI0.74-1.05
P =0.17
0
5
10
15
20
25
Cumulative
Incidence
(%)
0 1 2
Years sinceRandomization
3
Worsening HeartFailure
(HF Hospitalization + Urgent HFVisit)
CardiovascularDeath
12%
RRR
21%
RRR

FORXIGA預防T2D心衰竭住院、
針對HFrEF、HFmrEF、HFpEF顯著減少死亡 *
ACEI or ARBHFrEF患者
FORXIGA10 mg
Metformin
糖尿病患者
合併風險因子
預防HF住院
18%CV死亡
49%腎臟惡化 17%總死亡
36%心衰住院
治療HFrEF減少死亡治療HFpEF減少死亡
HFmrEF患者
HFpEF患者
HFmrE
F
12%CV死亡
21%HF惡化

T2Dpatients
T2Dpatients
StartJardiance®early to manage the CRM systems
CKD patients
PC-TW-105332-
20230609
SGLT-2 inhibitors are recommended by multiple practice guidelines globally,
including ADA, DAROC, ESC/EASD, KDIGO
1-4
HF patients
+ Preserved

EMPA-REG OUTCOME
Jardiance® CV outcome on T2Dpatients
Zinman B, et al. N Engl J Med. 2015 Nov 26;373(22):2117-28.
CV, cardiovascular; HHF, hospitalization for heart failure; MACE, major adverse cardiovascular events; MI, myocardial infarction; T2D, type 2 diabetes.
Aim: to examine the long-term effects of empagliflozin versus placebo, on top of standard of
care, on CV morbidity and mortality in patients with T2D and established CV disease
Screening
(n=11,531)
2-week
placebo run-in
Randomized
and treated
(n=7,020)
Placebo + standard of care
Empagliflozin 10 mg + standard of care
Empagliflozin 25 mg + standard of care
week
12
Stable background
glucose-lowering therapy
Background glucose-lowering therapy adjustment
allowed to achieve best care according to local
guidelines
Pooled for
statistical
analysis
Median study drug exposure: 2.6 years
Median observation time: 3.1years
772 primary events
*
Randomization
(1:1:1)
Double-blind
End of treatment
Any additional treatment considered necessary for the
patient’s welfare may be given at the discretion of the
investigator
Primary outcome 3P-MACE (CV death, non-fatal MI or non-fatal stroke)
Selected secondary and
exploratory outcomes
4P-MACE (CV death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina),
CV death, all-cause mortality, HHF, HHF+ CV death
PC-TW-105332-
20230609

95
InEMPA-REG OUTCOME
®
, Jardiance
®
showed
CV and renal benefits in people with T2Dand CVdisease
14%
RRRIN
3P-MACE
39%
RRRIN INCIDENT OR
WORSENING
NEPHROPATHY
35%
RRRIN HHF
38%
RRRIN
CV DEATH
HR 0.62
95% CI 0.49, 0.77
p<0.001
1
HR 0.65
95% CI 0.50, 0.85
p=0.002
1
HR 0.61
95% CI 0.53, 0.70
p<0.001
2
HR 0.86
95% CI 0.74, 0.99
p=0.04
32%
RRRIN ACM
HR 0.68
95% CI 0.57, 0.82
p<0.001
2 1
56%
Asian
32%
Asian
Global
Asian

EMPRISE
Jardiance®real-worldCV outcomes in T2Dpatients
KarasikA et al. ADA 2021; poster 127-LB
*The study period varied by country.
ACM, all-cause mortality, CI, confidence interval; CV, cardiovascular; DPP-4i, dipeptidyl peptidase-4 inhibitor; HHF, hospitalization for heart failure; HR, hazard ratio; MI, myocardial infarction.
Large administrative
databases and registers in
Finland, Germany, Israel,
Spain, Sweden, Japan, South
Koreas and Taiwan
Study period 2014-2019
*
Adult ≥18 years with type 2
diabetes newly initiating
empagliflozinor DPP-4i
1:1logistic-
regression
based
propensity
score
matching
“As treated”
exposure
time
HRs
generated
for each
country
using cox
proportiona
l hazards
models
Pooled HRs
with 95% CI
computed
using
random-
effects
meta-
analysis
models
•Two subgroup analyses in patients with and without history of CV
disease
•The individual CV effectiveness outcomes were: HHF, MI, stroke
and ACM
–Two composite outcomes: 1) HHF and ACM, and 2) MI,
stroke, and ACM.
•The safety outcomes were lower-limb amputation, bone fracture,
diabetic ketoacidosis and acute kidney injury that required dialysis.
PC-TW-105332-
20230609
: 78,144

EMPRISE East Asia
Jardiance®in East Asian T2Dpatients
Medical
Data Vision
National
Health Insurance
National
Health
Insurance Service
Dec 2014–
Apr 2018
May 2016–
Dec 2017
May 2016–
Dec 2017
1:1 propensity score-matched based on >130–149 baseline covariates
Jardiance®
(n=28,712)
DPP-4i
(n=28,712)
or
Follow-up
•Started the day after treatment initiation and continued in an “as-treated” approach
•Mean follow-up: 5.7 months in Japan, 6.8 months in South Korea, 5.9 months in
Taiwan
Seino Y, et al. Endocrinol Diabetes Metab. 2020 Sep 16;4(1):e00183.
*Diagnosis coding varied by country, a sensitivity analysis was conducted based on local coding practices
Patients with T2D and their clinical outcomes were identified using the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10)
DPP-4i, dipeptidyl peptidase-4 inhibitor; HF, heart failure; HHF, hospitalization for heart failure; T2D, type 2 diabetes.
Effectiveness
outcomes:
•HHF
defined as a HF discharge diagnosis in any position (HHF-
broad, main outcome) or in the primary position* (HHF-specific)
•All-cause
mortality
PC-TW-105332-
20230609
: 57,424
N=14,048

98
In EMPRISE(Global&EastAsia)OUTCOME
®
, Jardiance
®
showed
CV and renal benefits in people with T2D
24%
RRRIN HHF
40%
RRRIN AKI
37%
RRRIN HHF
42%
RRRIN ACM
40%
RRRIN ACM
18%18%
East Asia East Asia
28% 40%
East Asia East Asia
CVD (+) CVD (+) CVD (-)
40%
RRRIN ESRD
East Asia
CVD (-)
East Asia
Global

Composite primary outcome
EMPA-KIDNEY-empagliflozin reduces the risk of kidney disease
progression or CV death in patients with CKD
*Between 15 May 2019 and 16 April 2021, 6609 patients were randomized;
†
Guideline-directed medical therapy;
‡
Other outcomes prespecified
CKD, chronic kidney disease; CV, cardiovascular; eGFR, estimated glomerular filtration rate
The EMPA-KIDNEY Collaborative Group. N EnglJ Med 2022; in press
Placebo
once daily + standard of care
†
Empagliflozin 10 mgonce daily
+ standard of care
† Kidney disease progression
Outcomes
CV deathOR
•Kidney function loss defined as:
✓Sustained reduction of ≥40%eGFR decline
✓Sustained eGFR<10 ml/min/1.73 m
2
•ESKD
•Renal death
Key secondary
outcomes
‡
•All-cause hospitalization
•First occurrence of hospitalization for heart
failure or CV death
•All-cause mortality
Event driven: 1070 primary outcomes: 90% power at
p<0.05 to detect an 18% relative risk reduction
Participants: 6609 Median follow-up: 2 yrs

Primary composite outcome
Kidney disease progression orCV death
Patients at risk, n
Placebo 3305 3250 3129 2243 1496 592
Empagliflozin3304 3252 3163 2275 1538 624
HR 0.72
(95% CI 0.64, 0.82)
P < 0.001
RRR
28%
0 0.5 1 1.5 2 2.5
30
10
0
Years of Follow-up
Empagliflozin 10 mg
Participants with Event (%)
Placebo40
20
Placebo N(%):
558 (16.9%)
Events/100 PY: 8.96
Empagliflozin N(%):
432 (13.1%)
Events/100 PY: 6.85 NNT=28*

Components of the primary outcome
101
Kidney disease progression CV death
Placebo3305 3256 3146 2361 1562 681
Empagliflozin3304 3256 3176 2398 1610 726
Study day
Patients at risk, n
HR 0.71
(95% CI 0.62–0.81)
p<0.0001
Estimated cumulative
incidence function (%)
30
20
10
0
180 360 540 720 9000
Placebo
Empagliflozin 10 mg
Placebo:
504 patients with event
Rate: 8.09/100 PY
Empagliflozin:
384 patients with event
Rate: 6.09/100 PY
3305 3282 3235 2387 1646 679
3304 3283 3239 2371 1649 689
0 0.5 1 1.5 2 2.5
0
Empagliflozin 10 mg
Participants with Event (%)
Placebo20
10
00.511.522.5
0
1
2
3
4
5
Years of Follow-up
HR 0.84
(95% CI 0.60–1.19)

Keysecondaryoutcome:
Patients at risk, n
Placebo 3305 3283 3241 2500 1705 775
Empagliflozin3304 3283 3245 2493 1719 798
HR 0.87
(95% CI 0.70, 1.08)
P=0.21
Nominal RRR13%
8
7
6
4
5
3
1
2
0
Probability of event (%)
Study day (Years)
0.5 1.0 1.5 2.0 2.50
Placebo
Empagliflozin 10 mg
Placebo:
167 patients with event
Rate: 2.58/100 PY
Empagliflozin:
148 patients with
event
Rate: 2.28/100 PY
Placebo
Empagliflozin 10 mg
8
7
6
5
4
3
2
1
0
Study day (Years)
0 0.5 1.0 1.5 2.0 2.5
Estimated cumulative
incidence function (%)
Placebo:
152 patients with event
Rate: 2.37/100 PY
Empagliflozin:
131 patients with event
Rate: 2.04/100 PY
HR 0.84
(95% CI 0.67, 1.07)
P=0.15
Nominal RRR16%
Placebo 3305 3262 3209 2458 1661 748
Empagliflozin3304 3268 3210 2457 1685 781
Patients at risk, n
All-cause mortalityFirst adjudicated HHFor CV death

Jardiance
®
would delay kidney failure by
26.6 years if initiated when eGFR is 85 ml/min/1.73 m
2
Beatriz Fernández-Fernandez et al.ClinicalKidney Journal, 2023, vol. 16, no. 8, 1187–119
*post hoc analysis
Delay 26.6Years
Placebo

EMPEROR-Reduced+ EMPEROR-Preserved
Jardiance® in HF patients regardless of diabetes
EMPEROR-Reduced
1
3,730 patients with HF with
reduced ejection fraction (LVEF ≤40%)
Median follow-up = 16 months (event-driven)
LVEF
50%
HFrEF HFmrEF HFpEF
40%
EMPEROR-Preserved
2
5,988 patients with HF with
preserved ejection fraction (LVEF >40%)
Median follow-up = 26.2 months(event-driven)
Study population
Patients aged ≥18 years,
chronic HF (NYHA class II–IV)
Placebo
+ SOC
†
Jardiance® 10 mg +
SOC
†
Both trials
COMPOSITE PRIMARY ENDPOINT
Time to first event of adjudicated CV death or adjudicated HHF
SECONDARY ENDPOINTS
•First and recurrent adjudicated HHF events
•Slope of change in eGFR (CKD-EPI) from baseline
1. Packer M, et al. N Engl J Med. 2020 Oct 8;383(15):1413-1424. 2. Anker SD, et al. N Engl J Med. 2021 Oct 14;385(16):1451-1461.
*Randomized, double-blind, placebo-controlled trials. †All appropriate treatments for heart failure or other medical conditions.
CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; CV, cardiovascular; eGFR, estimated glomerular filtration rate; HF, heart failure; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection
fraction; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; SOC, standard of care.
+ Preserved
PC-TW-105332-
20230609
+ Preserved

-0.55
-1.25
-2.28
-2.62
-3
-2.5
-2
-1.5
-1
-0.5
0
Jardiance protected the kidneyby slowingthe decline in renal
function in patients with HF
Annual mean change in eGFR slope
Adjusted mean eGFR slope
(mL/min/1.73 m
2
)/year
Standard of care*
+ empagliflozin
Standard of care*
+ placebo
-0.55
2–4xslower decline
in kidney function
with empagliflozin
vs placebo
EMPEROR-Preserved
2
LVEF >40%
EMPEROR-Reduced
1
LVEF ≤40%
4x
protection
2x
protection
+ Preserved

EMPEROR-Reduced
HR 0.75; 95% CI 0.65, 0.86;p<0.001
ARR=5.3%; NNT=19
25%
RRRIN CV DEATH
OR HHF*
1
Jardiance
®
provides protection for people with HF across the
LVEFspectrum by reducing the risk of CV death or HHF
EMPEROR-Preserved
HR 0.79; 95% CI 0.69, 0.90;p<0.001
ARR=3.3%; NNT=31
21%
RRRIN CV DEATH
OR HHF
†2
Consistent efficacy across subgroups
including
1–3
:
•With or without T2D
•With or without CKD
HFrEF HFpEF
+ Preserved

107
Jardiance
®
provides triple protectionby reducing riskfor a broad
range of your patients with
1
:
25%
RRR IN
CV DEATH
or HHF
IN LVEF ≤40%
†1,3
21%
RRR IN
CV DEATH
or HHF
IN LVEF >40%
‡1,4
HF**
HFrEF HFpEF
HR 0.75; 95% CI 0.65, 0.86;
p<0.001ARR 5.3% NNT 19
HR 0.79; 95% CI 0.69, 0.90;
p<0.001 ARR 3.3% NNT 30
In addition, Jardiance
®
provides metabolic benefits in T2D, including reductions in
HbA1c, systolic blood pressure and weight
¶1,6
28%
CKD**
HR 0.72; 95% CI 0.64, 0.82;
p<0.001 ARR 3.8% NNT 26
38%
RRR IN
CV DEATH *
1,2
T2D & CVD**
HR 0.62; 95% CI 0.49, 0.77;
p<0.001 ARR 2.2% NNT 46
%
RRR IN
HHF
‡7
T2D
without CVD history*
HR 0.63; 95% CI 0.47, 0.84;
p<0.001
37
RRR IN
KIDNEY DISEASE
PROGRESSION
or CVDEATH
§5

SGLT2i預防糖尿病腎病、治療 CKD
遠離洗腎、降低死亡
ACEI or ARBCKD患者
SGLT-2 inhibitor
Metformin糖尿病患者
EMPAKIDNEY DAPACKD
13%總死亡
29%腎臟惡化
33%ESRD
44%腎臟惡化
36%ESRD
31%總死亡

PooledHF meta-analysis
No: 21947
SGLT-2 inhibitor
No: 11007
13%CV死亡14% CV死亡
28% HF住院29% HF住院
DAPA-HF&DELIVER
DAPA-HF&
EMPEROR-Reduced
DAPA-HF & DELIVER
EMPEROR-R& EMPEROR-P
SOLOIST-WHF
DELIVER &
EMPEROR-Preserved
No: 8474 No: 12251
14% CV死亡 12% CV死亡
31% HF住院 26% HF住院
HFrEF HFpEF HFpEFHFrEF+
DAPA

優質控糖:↓ A1c、改善胰島素敏感性及 β細胞功能
降低白蛋白尿 ,↓all-cause mortality, 3P-MACE,HHFand CV death
啟用於eGFR≥25 or 30 ml/min/1.73 m
2
並續用至洗腎
↓ Urate
針對糖尿病合併 CKD:
2024 ADA&EASD最新共識、 ADA及KDIGODKD聯合聲明、中華民國糖尿病學會第 2型糖尿病臨床照護
指引、台灣腎臟醫學會等最新指引建議 :
eGFR<60或UACR≥30的T2D患者建議優先使用 SGLT-2抑制劑，首選具有腎病變實證的SGLT2i
2. 針對糖尿病合併 HF:
2023 AHA/ACC/ESC 報告:
ESC recommend SGLT2inhibitorsasfirst-line HFrEFtherapy
SGLT2ishould be initiated in all HFpEFpatients without contraindications
SGLT2i從心衰竭預防到治療扮演重要角色
中華民國糖尿病學會第 2型糖尿病臨床照護指引 :SGLT2i可減少因心臟衰竭住院的風險
Conclusion
2
3
SGLT2i
1SGLT2i針對糖尿病 :Metabolic

SGLT2ieGFR (<45) limitation updates

Dapagliflozin 5/10 mg Empagliflozin 10/25 mg Canagliflozin 100 mgErtugliflozin 5/15 mg
適
應
症
第二型糖尿病
血糖控制：
配合飲食和運動，以改善第二型糖尿病成人的血
糖控制。
預防心血管事件：
用於具第二型糖尿病且已有心血管疾病 (CVD)或
多重心血管風險因子的成人病人時，可降低心衰
竭住院的風險。
預防腎臟病：
降低慢性腎臟病 (CKD)新發生或惡化的風險。
心衰竭[HFrEF已健保給付 ]
用於心衰竭的成人病人時，可降低心血管死亡、
心衰竭住院和心衰竭緊急就醫的風險。
慢性腎臟病
用於治療有惡化風險之慢性腎臟病的成人病人時，
可降低持續性腎絲球過濾率 (eGFR)下降、末期腎
病(ESKD)、心衰竭住院和心血管死亡的風險。
第二型糖尿病
血糖控制
第二型糖尿病。
預防心血管事件
用於具第二型糖尿病且已有心血
管疾病的成人病人時，可降低心
血管原因死亡的風險。
心臟衰竭 [10 mgonly]
用於紐約心臟學會 (NYHA)第二級
至第四級的心臟衰竭成人病人，
可：(1)降低心血管死亡和心臟衰
竭住院風險。(2)減緩預估腎絲球
過濾率(eGFR)下降。
慢性腎臟病 [10mgonly]
第二型糖尿病
糖尿病腎病變
(巨量蛋白尿期 )
第二型糖尿病
適用於配合飲食控制及
運動，以改善第二型糖
尿病成人病人的血糖控
制。
112/8/15
New Indication of SGLT2iin Taiwan
適用於患有慢性腎臟病的成人病人，以降低以下風險：
-腎臟疾病惡化（預估腎絲球過濾率 (eGFR)持續降低、末期腎臟疾病或腎
臟死亡）或心血管死亡
-全因性住院
1110801
1120822

What we meet in T2Dtreatment
DPP4i
SGLT2i
GLP-1RA
Beyond medication: how new technology to support DM patient
management(case sharing)
Outline

PHARMACOLOGICAL EFFECTS OF GLP -1RAs
GLP-1RAshave multifactorial effects
Pancreas (beta cell)
beta-cell function
1
Insulin biosynthesis
1
Glucose-dependent glucagon
secretion
1
GI tract
Gastric emptying
6
Pancreas (alphacell)
Glucagon secretion
1
Lipotoxicity
7
Brain
Body weight
2
Food intake
3
Satiety
4,5
Kidneys
Natriuresis
1
Muscles
Insulin sensitivity
7
Hyperglycaemia
Liver
Hepatic glucose production
7
Hepatic insulin sensitivity
7
De novolipogenesis
7
Steatosis
8
T2D

GLP-1RAs vary in molecular structureand size
*Withdrawn from market.
GLP-1, glucagon-like peptide-1; GLP-1RA, glucagon-like peptide-1 receptor agonist; IgG4 Fc, immunoglobulin-G4 fragment crystallisable; kDa, kilodalton. Full reference list can be found in the slide notes.
Liraglutide(3.75 kDa, 97% homology)
HisAla ThrThrSerPheGluGly Asp
Val
Ser
SerTyrLeuGluGlyAlaAlaGlnLys
Glu
Glu
Phe
IleAlaTrpLeu GlyValGlyArgArg
Semaglutide (4.11 kDa, 94% homology)
HisAib ThrThrSerPheGluGly Asp
Val
Ser
SerTyrLeuGluGlyAlaAlaGln
Phe
Lys
Glu
IleAlaTrpLeu GlyValGlyArgArg
Lixisenatide(4.86 kDa, ~50% homology)
HisGly ThrThrSerPheGluGly Asp
Leu
Ser
LysGlnMetGluGluAlaValGluArg
Phe
Leu
IleGluTrpLeu ProLysGlyGlyAsp SerSerGlyAlaProProProSer
HisGly ThrThrSerPheGluGly Asp
Leu
Ser
LysGlnMetGluGluAlaValGluArg
IleGluTrpLeu ProLysGlyGlyAsp SerSerGlyAlaProProProSerLys
Lys
Lys
LysLysLys
Phe
Leu
Exenatide(4.19 kDa, 53% homology) Dulaglutide(~63 kDa, 90% homology)
HisGly ThrThrSerPheGluGly AspVal
Ser
SerTyrLeuGluGluAlaAlaGlnLys
Phe
Glu
IleAlaTrpLeu GlyValGlyGlyLys
PheIleAlaTrpLeu GlyValGlyGlyLys
Glu
SerTyrLeuGluGluAlaAlaGlnLys
Ser
HisGly ThrThrSerPheGluGly AspVal
Linker
peptide
Modified IgG4
Fc domain
Exendin-based GLP-1RAs
HumanGLP-1 analogues
Small Large
Albiglutide*
HisGly ThrThrSerPheGluGly AspValSerSerTyrLeuGluGlyAla
Ala
Gln
Lys
PheGluIleAlaTrpLeuGly ValGlyArgLysHisGlyThrThr
Ser
Phe GluGly
Asp
Val
SerSerTyrLeuGluGlyAlaAlaGln LysPheGluIleAlaTrp
Leu
Asp
Val
Gly
Arg
Lys
ALBUMIN

CVOTs investigating GLP-1RAtherapies in T2D
20192015 20202014 2016 2017 2018
LEADER, SUSTAIN 6and HARMONY outcomes have demonstrated CV risk reduction
in high-risk T2D populations
Completed trials
FREEDOM
4,5
(ITCA 650, GLP-1RA in DUROS)
n=4,156; duration ~2 years
Q2 2016 –TOPLINE RESULTS
ELIXA
1
(Lixisenatide, GLP-1RA)
n=6,068; follow-up ~2 years
Q1 2015 –RESULTS
REWIND
7
(Dulaglutide, OW GLP-1RA)
n=9,901; duration ~6.5 years
Q3 2018 –TOPLINE RESULTS
SUSTAIN 6
3
(Semaglutide, OW GLP-1RA)
n=3,297; duration ~2.8 years
Q3 2016 –RESULTS
LEADER
2
(Liraglutide, GLP-1RA)
n=9,340; duration 3.5–5 years
Q2 2016 –RESULTS
EXSCEL
6
(Exenatide ER, OW GLP-1RA)
n=14,752; follow-up ~3 years
Q3 2017 –RESULTS
HARMONY OUTCOMES
*
(Albiglutide, OW GLP-1RA)
n=9,463; duration ~1.6 years
Q3 2018 –RESULTS
PIONEER 6
9
(Oral semaglutide, GLP-1RA)
n=3,183; duration ~1.5 years
Q4 2018 –RESULTS
AMPLITUDE-O
10
(Efpeglenatide, OW GLP-1RA)
n=4,000*; duration ~3 years
Q2 2021 –COMPLETION
Ongoing trials
Completed trials with
positive outcomes

Endothelial cell
NO
ROS
Inflammation
Intestine
ApoB48
TAG secretion
FFAsecretion
ApoB48, apolipoprotein B-48; FFA, free fatty acid; GLP-1, glucagon-like peptide-1; NO, nitric oxide; ROS, reactive oxygen species; TAG, triacylglycerol.
Ussher JR and Drucker DJ. EndocrRev 2012;33:187–215.
Brain
Appetite
Lipid
CD36
Inflammation
Macrophage
foam cell
Reduction in
atherosclerotic
plaque
Proliferation
Smooth
muscle cell
GLP-1
Anti-Atherosclerotic Potential of GLP-1

2024 ADA guideline
Pharmacologic treatment of hyperglycemia in adults with T2D
ACEi, angiotensin-converting enzyme inhibitor; ACR, albumin/creatinine ratio; ARB, angiotensin receptor blocker; ASCVD, atherosclerotic cardiovascular disease; CGM, continuous glucose monitoring; CKD, chronic kidney disease; CV,
cardiovascular; CVD, cardiovascular disease; CVOT, cardiovascular outcomes trial; DPP-4i, dipeptidyl peptidase 4 inhibitor; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HF, heart failure;
HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; MACE, major adverse cardiovascular events; MI, myocardial infarction; SDOH, social
determinants of health; SGLT-2i, sodium-glucose cotransporter 2 inhibitor; T2D, type 2 diabetes; TZD, thiazolidinedione. Standards of Care in Diabetes -2024: Diabetes Care, December 2023, Vol.47, Supplement 1; Figure 9.3
Very High:
Semaglutide, Tirzepatide
High:
Dulaglutide, Liraglutide
Intermediate:
GLP-1 RA (not listed above), SGLT-2i
Neutral
DPP-4i, Metformin
USE OF GLUCOSE-LOWERING MEDICATIONS IN THE MANAGEMENT OF T2D
HEALTHY LIFESTYLE BEHAVIORS: DIABETES SELF-MANAGEMENT, EDUCATION AND SUPPORT (DSMES); SOCIAL DETERMINANTS OF HEALTH (SDOH)
Goal: Cardiorenal Risk Reduction in High-Risk individuals with T2D
(in addition to comprehensive CV risk management)*
+ASCVD/Indicators of high risk
GLP-1 RA
#
with proven
CVD benefit
SGLT-2i
§
with proven
CVD benefit
Either/
OR
If HbA
1C above target
•For patients on a GLP-1 RA, consider adding SGLT-2i with proven CVD
benefit and vice versa
•TZD^
If additional cardiorenal risk reduction or glycemic lowering needed
+ HF
SGLT-2i
§
with proven HF
benefit in this
population
+ CKD (on maximally tolerated
dose of ACEi/ARB)
PREFERABLY
SGLT-2i
§
with primary evidence
of reducing CKD progression
Use SGLT-2i in people with an eGFR ≥ 20 ml/min per 1.73 m
2
,
once initiated should be continued until initiation of dialysis or
transplantation
OR
GLP-1 RA with proven CVD benefit if SGLT-2i not tolerated or
contraindicated
If HbA
1Cabove target, for patients on SGLT-2i, consider
incorporating a GLP-1 RA or vice versa
Goal: Achievement and Maintenance of Glycemic and Weight Management Goals
Glycemic Management: Choose approaches that
provide the efficacy to achieve goals:
Metformin OR Agent(s) including COMBINATION therapy that
provide adequate EFFICACY to achieve and maintain
treatment goals
Prioritize avoidance of hypoglycemia in high-risk individuals
Very High:
Dulaglutide (high dose), Semaglutide, Tirzepatide
Insulin
Combination Oral, Combination Injectable
(GLP-1 RA/Insulin)
High:
GLP-1 RA (not listed above), Metformin, SGLT-2i,
Sulfonylurea, TZD
Intermediate:
DPP-4i
Achievement and maintenance of weight managementgoals:
Set individualized weight management goals
General lifestyle advice: medical
nutritional therapy/ eating
patterns/ physical activity
Intensive evidence-based
structured weight management
program
Consider medication for weight
loss
Consider metabolic surgery
When choosing glucose-lowering therapies:
Consider regimen with high-to-very high dual glucose and weight
efficacy
Efficacy for weight loss
If HbA
1cabove target
Identify barriers to goals:
•Consider DSMES referral to support self-efficacy in achievement of goals
•Consider technology (e.g. diagnostic CGM) to identify therapeutic gaps and tailor therapy
•Identify and address SDOH that impact on achievement of goals
+ASCVD
†
Defined differently across CVOTs but
all included individuals with established CVD (e.g. MI,
stroke, any revascularization procedure). Variably
included: conditions such as transient ischemic
attack, unstable angina, amputation, symptomatic or
asymptomatic coronary artery disease.
+Indicators of
high risk
While definitions vary, most
comprise ≥ 55 years of age with two
or more additional risk factors
(including obesity, hypertension,
smoking, dyslipidemia, or
albuminuria)
+HF
Current or prior symptoms
of HF with documented
HFrEFor HFpEF
+CKD
eGFR < 60 ml/min per 1.73 m
2
OR albuminuria (ACR ≥ 3.0
mg/mmol (30mg/g)). These measurements may vary over time;
thus, a repeat measure is required to document CKD.
*In people with HF, CKD, established CVD or multiple risk factors for CVD, the decision to use a GLP-1 RA or SGLT-2i with provenbenefit should be independent of
background use of metformin;
†
A strong recommendation is warranted for people with CVD and a weaker recommendation for those with indicators of high CV risk.
Moreover, a higher absolute risk reduction and thus lower numbers needed to treat are seen at higher levels of baseline risk andshould be factored into shared decision-
making process. ^Low-dose TZD may be better tolerated and similarly effective; §For SGLT-2i, CV/renal outcomes trials demonstrate their efficacy in reducing the risk of
composite MACE, CV death, all-cause mortality, MI, HHF and renal outcomes in individuals with T2D with established/high risk of CVD; # For GLP-1 RA, CVOTs
demonstrate their efficacy in reducing composite MACE, CV death, all-cause mortality, MI, stroke and renal endpoints in individuals with T2D with established/high risk of
CVD.
In general, higher efficacy approaches have greater likelihood
of achieving
glycemic goals
Efficacy for glucose lowering
TO AVOID THERAPEUTIC
INERTIA REASSESS AND
MODIFY TREATMENT
REGULARLY
(3-6 MONTHS)
Chapter 09
To see an expanded version of each box, click on it

Very High:
Semaglutide, Tirzepatide
High:
Dulaglutide, Liraglutide
Intermediate:
GLP-1 RA (not covered above), SGLT2i
Neutral
DPP-4i, Metformin
USE OF GLUCOSE LOWERING MEDICATIONS IN THE MANAGEMENT OF TYPE 2 DIABETES
HEALTHY LIFESTYLE BEHAVIOURS: DIABETES SELF-MANAGEMENT, EDUCATION AND SUPPORT (DSMES); SOCIAL DETERMINANTS OF HEALTH (SDOH)
Goal: Cardiorenal Risk Reduction in High-Risk Patients with Type 2 Diabetes
(in addition to comprehensive CV risk management)*
+ ASCVD/Indicators of high risk
GLP-1 RA
#
with proven
CVD benefit
SGLT2i
§
with proven
CVD benefit
Either/
OR
If HbA
1C above target
•For patients on a GLP-1 RA, consider adding SGLT-2i with proven CVD
benefit and vice versa
•TZD^
If additional cardiorenal risk reduction or glycaemiclowering needed
+ HF
SGLT2i
§
with proven HF
benefit in this
population
+ CKD (on maximally tolerated
dose of ACEi/ARB)
PREFERABLY
SGLT-2i
§
with primary evidence
of reducing CKD progression
Use SGLT2i in people with an eGFR ≥ 20 ml/min per 1.73 m
2
,
once initiated should be continued until dialysis or
transplantation
OR
GLP-1 RA with proven CVD benefit if SGLT2i not tolerated or
contraindicated
If HbA
1Cabove target, for patients on SGLT2i, consider
incorporating a GLP-1RA or vice versa
Goal: Achievement and Maintenance of Glycaemicand Weight Management Goals
GlycaemicManagement: Choose approaches that
provide the efficacy to achieve goals:
Metformin OR Agent(s) including COMBINATION therapy that
provide adequate EFFICACY to achieve and maintain
treatment goals
Consider avoidance of hypoglycaemiaa priority in high-risk
individuals
Very High:
Dulaglutide (high dose), Semaglutide, Tirzepatide
Insulin
Combination Oral, Combination Injectable
(GLP-1 RA/Insulin)
High:
GLP-1 RA (not listed above), Metformin, SGLT2i, Sulfonylurea,
TZD
Intermediate:
DPP-4i
Achievement and Maintenance of Weight ManagementGoals:
Set individualized weight management goals
General lifestyle advice: medical
nutritional therapy/ eating
patterns/ physical activity
Intensive evidence-based
structured weight management
program
Consider medication for weight
loss
Consider metabolic surgery
When choosing glucose-lowering therapies:
Consider regimen with high-to-very high dual glucose and weight
efficacy
Efficacy for weight loss
If HbA
1cabove target
Identify barriers to goals:
•Consider DSMES referral to support self-efficacy in achievement of goals
•Consider technology (e.g. diagnostic CGM) to identify therapeutic gaps and tailor therapy
•Identify and address SDOH that impact on achievement of goals
+ HF
Current or prior symptoms
of HF with documented
HFrEFor HFpEF
+CKD
eGFR < 60 ml/ min per 1.73 m
2
OR albuminuria (ACR ≥ 3.0
mg/mmol (30mg/g)). These measurements may vary over time;
thus, a repeat measurement is required to document CKD.
* In people with HK, CKD and established CVD or multiple risk factors for CVD, the decision to use a GLP-1 RA or SGLT2i with proven benefit should be independent of
background use of metformin; † A strong recommendation is warranted for people with CVD and a weaker recommendation for thosewith indicators of high CV risk.
Moreover, a higher absolute risk reduction and thus lower numbers needed to treat are seen at higher levels of baseline risk andshould be factored into shared decision-
making process. ^ Low-dose TZD may be better tolerated and similarly effective; §For SGLT2i, CV/renal outcomes trials demonstrate their efficacy in reducing the risk of
composite MACE, CV death, all-cause mortality, MI, HHF and renal outcomes in individuals with T2D with established/high risk of CVD; # For GLP-1 RA, CVOTs
demonstrate their efficacy in reducing composite MACE, CV death, all-cause mortality, MI, stroke and renal endpoints in individuals with T2D with established/high risk of
CVD.
In general, higher efficacy approaches have greater likelihood
of achieving
glycaemicgoals
Efficacy for glucose lowering
TO AVOID CLINICAL
INERTIA REASSESS AND
MODIFY TREATMENT
REGULARLY
(3-6 MONTHS)
+ ASCVD/Indicators of high risk
GLP-1 RA
#
with proven
CVD benefit
SGLT2i
§
with proven
CVD benefit
Either/
OR
GLP-1 RAs or SGLT-2is recommended 1
st
line
independent of metformin for individuals with T2D with
established ASCVD(including stroke and TIA) or
indicators of high risk
ACEi, angiotensin-converting enzyme inhibitor; ACR, albumin/creatinine ratio; ARB, angiotensin receptor blocker; ASCVD, atherosclerotic cardiovascular disease; CGM, continuous glucose monitoring; CKD,
chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; CVOT, cardiovascular outcomes trial; DPP-4i, dipeptidylpeptidase 4 inhibitor; eGFR, estimated glomerular filtration rate; GLP-1 RA,
glucagon-like peptide 1 receptor agonist; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heartfailure with reduced ejection fraction; HHF, hospitalization for heart failure; MACE,
major adverse cardiovascular events; MI, myocardial infarction; SDOH, social determinants of health; SGLT2i, sodium-glucose cotransporter 2 inhibitor; T2D, type 2 diabetes; TZD, thiazolidinedione. Davies MJ. et
al, Diabetes Care 2022; https://doi.org/10.2337/dci22-0034
+ASCVD
†
Defined differently across CVOTs but
all included individuals with established CVD (e.g. MI,
stroke, any revascularization procedure). Variability
included: conditions such as transient ischaemic
attack, unstable angina, amputation, symptomatic or
asymptomatic coronary artery disease.
+Indicators of
high risk
While definitions vary, most
comprise ≥ 55 years of age with two
or more additional risk factors
(including obesity, hypertension,
smoking, dyslipidaemiaor
albuminuria)
2024 ADA guideline

SGLT-2iGLP-1
Established CVDor CKD
ASCVD
or
SUTZD
DPP-4i
Basal
insulin
or
or
or
If HbA
1cabove target
…with proven CVD benefit
Heart failureor CKD
SGLT-2i
GLP-1
or
…with demonstrated CV safety
Preferably
GLP-1RAs recommended when there is a need to minimisehypoglycaemia
or weight gain, or when ASCVD/CKD predominate
ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; DPP-4i, dipeptidyl peptidase-4 inhibitor; GLP-1, glucagon-like peptide-1; GLP-1RA, glucagon-like peptide-1 receptor
agonist; SGLT2i, sodium-glucose cotransporter-2 inhibitor; SU, sulphonylurea; TZD, thiazolidinedione.
Davies M et al. Diabetes Care 2018;41:2669–701.
Target:
HbA
1c<7%
Cost issue
TZD
or
Basal
insulin
or
DPP-4i SGLT-2ior
SU
If HbA
1cabove target
Intensify with combinations
If HbA
1cabove target
…with lowest acquisition cost
Weightconcern
SGLT-2iGLP-1
DPP-4i
Intensify with combinations
If HbA
1cabove target
or
…with good efficacy for weight loss
If HbA
1cabove target
or cautious use of
SU
TZD
Basal
insulin
or
Preferably
or
Withoutestablished CVD or CKD
TZD
SGLT-2i GLP-1
or
or
or
Basal
insulin
or SU
Intensify with combinations
except for DPP-4i and GLP-1 combinations
DPP-4i
If HbA
1cabove target
If HbA
1cabove target
…with lower risk of hypoglycaemia
Hypoglycaemic concern
MetforminFirst line therapy + weight management and physical activity
If HbA
1cis above target…

GLP-1 RAs Cardiovascular
Outcome Trials (CVOTs)

Meta-Analysis of GLP-1 RA CVOTs
Three-point MACE
GLP-1 RA, n/N (%)
Placebo
n/N (%)
Hazard ratio
(95% CI)
NNT
(95% CI)
pvalue
Three-point MACE
ELIXA 400/3034 (13%) 392/3034 (13%) 1.02 (0.89-1.17) 0.78
LEADER 608 (4668 (13%) 694/4672 (15%) 0.87 (0.78-0.97) 0.01
SUSTAIN-6 108 (1648 (7%) 146/1649 (9%) 0.74 (0.58-0.95) 0.016
EXSCEL 839/7356 (11%) 905/7396 (12%) 0.91 (0.83-1.00) 0.061
Harmony Outcomes 338/4731 (7%) 428/4732 (9%) 0.78 (0.68-0.90) 0.0006
REWIND 594/4949 (12%) 663/4952 (13%) 0.88 (0.79-0.99) 0.026
PIONEER 6 61/1591 (4%) 76/1592 (5%) 0.79 (0.57-1.11) 0.17
AMPLITUDE-O 189/2717 (7%) 125/1359 (9%) 0.73 (0.58-0.92) 0.0069
Subtotal (I
2
=44.5%, p=0.082) 0.86 (0.80-0.93)65 (45-130)<0.0001
0.5 1 1.5
Favours GLP-1 receptor agonistsFavours placebo

Meta-Analysis of GLP-1 RA CVOTs
Cardiovascular death
GLP-1 RA, n/N (%)
Placebo
n/N (%)
Hazard ratio
(95% CI)
NNT
(95% CI)
pvalue
Cardiovascular death
ELIXA 156/3034 (5%) 158/3034 (5%) 0·98 (0·78–1·22) 0·85
LEADER 219/4668 (5%) 278/4672 (6%) 0·78 (0·66–0·93) 0·007
SUSTAIN-6 44/1648 (3%) 46/1649 (3%) 0·98 (0·65–1·48) 0·92
EXSCEL 340/7356 (5%) 383/7396 (5%) 0·88 (0·76–1·02) 0·096
Harmony Outcomes 122/4731 (3%) 130/4732 (3%) 0·93 (0·73–1·19) 0·58
REWIND 317/4949 (6%) 346/4952 (7%) 0·91 (0·78–1·06) 0·21
PIONEER 6 15/1591 (1%) 30/1592 (2%) 0·49 (0·27–0·92) 0·021
AMPLITUDE-O 75/2717 (3%) 50/1359 (4%) 0·72 (0·50–1·03) 0·07
Subtotal (I²=13·4%, p=0·33) 0·87 (0·80–0·94)163 (103–353) 0·0010
0.5 1 1.5
Favours GLP-1 receptor agonistsFavours placebo

Meta-Analysis of GLP-1 RA CVOTs
Fatal or non-fatal MI
GLP-1 RA, n/N (%)
Placebo
n/N (%)
Hazard ratio
(95% CI)
NNT
(95% CI)
pvalue
Fatal or non-fatal MI
ELIXA 270/3034 (9%) 261/3034 (9%) 1·03 (0·87–1·22) 0·71
LEADER 292/4668 (6%) 339/4672 (7%) 0·86 (0·73–1·00) 0·046
SUSTAIN-6 54/1648 (3%) 67/1649 (4%) 0·81 (0·57–1·16) 0·26
EXSCEL 483/7356 (7%) 493/7396 (7%) 0·97 (0·85–1·10) 0·62
Harmony Outcomes 181/4731 (4%) 240/4732 (5%) 0·75 (0·61–0·90) 0·003
REWIND 223/4949 (5%) 231/4952 (5%) 0·96 (0·79–1·15) 0·63
PIONEER 6 37/1591 (2%) 35/1592 (2%) 1·04 (0·66–1·66) 0·49
AMPLITUDE-O 91/2717 (3%) 58/1359 (4%) 0·75 (0·54–1·05) 0·09
Subtotal (I²=26·9%, p=0·21) 0·90 (0·83–0·98)175 (103–878) 0·020
Favours GLP-1 receptor agonistsFavours placebo
0.5 1 1.5

Human-Based GLP-1RAs Decreased the Risk of Coronary
Revascularizationby 11%
B. Subgroup---exendin based VS. human-based
Xueyuanet al. Diabetes ObesMetab. 2023 Apr;25 Suppl 1:53-63. doi: 10.1111/dom.15043. Epub2023 Mar 31.

A Meta-Analysis of GLP-1RA CVOTs Showed a Significant
17%Risk Reduction for Stroke*
*Fatal or non-fatal stroke.
CI, confidence interval; CVOT, cardiovascular outcomes trial; GLP-1RA, glucagon-like peptide-1 receptor agonist.
Kristensen SL et al. Lancet Diabetes Endocrinol 2019;7:776–85.

Qingyanget al. BMJ. 2023 Apr 6;381:e074068. doi: 10.1136/bmj-2022-074068.
Benefits and Harms of SGLT-2isand GLP-1 RAs
GLP-1 receptor agonists SGLT-2 inhibitors

GLP-1 RAs RWE

In the “ITT” approach, patients were followed from the index date to the event, death, or the last available observation, whichever occurred first.
In the “as treated” (AT) approach, the observation was stopped in case patients discontinued treatment with GLP-1RA or BI
Enrico et al. CardiovascDiabetol. 2021 Nov13;20(1):222. doi: 10.1186/s12933-021-01414-3
Italy database (Administrative claims database of the Veneto Region; 2014~2018)
GLP-1RAs Had Better Cardiovascular Outcomes than
Basel Insulin in Patients with T2D
56%
33%
41%

David Liu et. al. Cardiovasc Diabetol. 2023 Feb 24;22(1):40. doi: 10.1186/s12933-023-01772-0.
GLP-1RAUse Was Associated with Lower Risk of Ischemic Stroke than
SGLT2iUse in Patients with T2D
Hong Kong Database (Electronic health records of Hong Kong Hospital Authority; 2008/01/01~2020/12/31)
Number of
case (%)
Incidence rate
per 100 person-
years (95%CI)
Person-
years
Median
follow-up
month (IQR)
Incidence rate
ratio (95% CI)
P-value
Hazard ratio
(95%CI)
P-value
All Stroke
All patients111 (1.9%)0.94 (0.78, 1.14)11771 17 (8-34)
SGLT2i 62 (2.1%)1.10 (0.86, 1.41)5621 19(8-35)1.38 (0.95, 2.01)0.089 1.46 (0.99, 2.17)0.058
GLP-1RA 49 (1.7%)0.80 (0.60, 1.05)6150 17(8-34)1 (Reference) 1 (Reference)
Hemorrhagic stroke
All patients23(0.4%)0.19(0.13, 0.29)11918 17 (8-34)
SGLT2i 11(0.4%)0.19 (0.11, 0.35)5683 19 (9-35)1.01 (0.44, 2.28)0.989 1.29 (0.53, 3.14)0.582
GLP-1RA 12(0.4%)0.19 (0.11, 0.34)6236 16 (7-32)1 (Reference) 1 (Reference)
Ischemic stroke
All patients98 (1.7%)0.83(0.68, 1.01)11780 17(8-34)
SGLT2i 57 (2.0%)1.01 (0.78, 1.31)5628 19(8-35)1.52(1.02, 2.27)0.041* 1.53 (1.01, 2.33)0.044*
GLP-1RA 41 (1.4%)0.67 (0.49, 0.91)6152 16(7-32)1 (Reference) 1 (Reference)
Cardioembolic stroke
All patients25 (0.4%)0.21 (0.14, 0.31)11906 17 (8-34)
SGLT2i 14 (0.5%)0.25 (0.15, 0.42)5676 19 (9-35)1.40 (0.60, 3.08)0.407 1.40 (0.62, 3.17)0.414
GLP-1RA 11 (0.4%)0.18 (0.10, 0.32)6230 16 (7-32)1 (Reference) 1 (Reference)
0.11.010.0
Favors SGLT2i Favors GLP-1 RA
0.11.010.0
Favors SGLT2i Favors GLP-1 RA

XI TAN, YUANJIE LIANG, JIGAR R. RAJPURA, LARISA YEDIGAROVA, JOSHUA NOONE, LIN XIE, ADAM DE HAVENON; 791 -P: Comparingthe Real-World Effectsof Once-Weekly GLP-
1 RAsand DPP-4 Inhibitorson IschemicStroke and MyocardialInfarctionin Individualswith T2D and ASCVD. Diabetes 20 June 2023; 72 (Supplement_1): 791–P.
GLP-1 RAs Are More Effective than DPP-4isin Reducing the Risks of
Ischemic Stroke and MIin Adults with T2D and ASCVD
US database (OptumClinformatics® Data Mart. 2017/01/01~ 2021/09/30)
24%

1. Strong evidence for the important role of GLP-1 in T2DMtreatment. All guidelines
recognize the beneficial CV effects of GLP-1 RA.
2. GLP-1RAsBoth Semaglutideof Ozempic®and Rybelsus®can meet
(a). Effective glycemic lowering ability
(b). Strong evidence of organs protection
(c). More options readily available with oral formulation
(d). Well tolerated with scheduled titration and education
3.In addition to treat T2DM, GLP-1 RA may be used for the patients with ASCVD
(including PAD) to get beneficial effects.
4.
Conclusion
GLP-1 RA
GLP-1RA

Effects of GLP-1 RA on CV Risk Factors/Outcomes and Practical Aspects
for the Use of These Agents
Conclusion(3)GLP-1RA

GLP-1RAeGFR(<45) limitation updates

What we meet in T2Dtreatment
DPP4i
SGLT2i
GLP-1RA
Beyond medication: how new technology to support DM patient
management(case sharing)
Outline

糖尿病管理工具的進步支持改善護理的解決方案
Dose recording and timely
data monitoring
technologies
Glucose monitoring
technologies
Gla-100, insulin glargine 100 U/mL; Gla-300, insulin glargine 300 U/mL; IDeg, insulin degludec; IDet, insulin detemir; NPH, Neutral Protamine Hagedorn. Pettus J, et al. Diabetes MetabRes Rev
2016;32:478–96; DanneT, et al. Diabetes Care 2017;40(12):1631–1640
Mallya cap
智抗糖APP
CGM

除了HbA1c，血糖變異性和TIR是支持有效糖尿病管理的關鍵指標
with T1DM
2
with T1DM
2
with T1DM
2
International
guidelines
recommend Time-in-Range
and glycemic variability
as key metrics to facilitate
effective diabetes
management
7,8
Glycemic variability
is a common challenge for
people with diabetes
1,2
Excessive
glycemic variability
and suboptimal
Time-in-Range
can significantly impact
the lives of people
with diabetes
3-6
HbA1c, hemoglobinA1c.
1. Monnier L, et al. Diabetes Care. 2017;40:832–838; 2. AgiostratidouG, et al. Diabetes Care. 2017;40:1622–1630; 3. Beck RW, et al. Diabetes Care. 2019;42:400–405; 4. MayedaL, et al. BMJ Open Diab
Res Care. 2020;8:e000991; 5. Lu J, et al. Lu J, et al. DiabetesCare. 2021;44:549–555; 6. BergenstalRM,et al.Presented at the American Diabetes Association, 80th Scientific Sessions; June 12–16, 2020.
21-L; 7.ADA. Diabetes Care. 2022;45(Suppl1); 8.BattelinoT, et al. Diabetes Care. 2019;42:1593–1603.

139
Better outcomes for
your patients
1,5–8
降低血糖變異性是有效管理 T1DM 和T2DM的基本要素
%CV, percentage coefficient of variation for glucose; QoL, quality of life; T1DM, Type 1 diabetes; T2DM, Type 2 diabetes; TIR, time-in-range
1. ADA. Diabetes Care. 2020;43(Suppl1); 2. Monnier L, et al. Diabetes Metab. 2018;44:97–100; 3. Rayman G. Br J Diabetes. 2016;16(Suppl1):S3-S6; 4. Battelino T, et al. Diabetes Care. 2019;42:1593–1603; 5. Runge AS, et al. Clin Diabetes. 2018;36:112–119;
6. Beck RW, et al. Diabetes Care. 2019;42:400–405; 7. Bergenstal RM, et al. Presented at the American Diabetes Association, 80th Scientific Sessions. June 12–16, 2020. 21-LB; 8. Lu J, et al. Diabetes Care. 2020; dc201862.doi:10.2337/dc20-1862 (Online ahead
of print).
Balance hyperglycaemia reduction
while avoiding hypoglycaemia
<7.0%
Increasing TIR and
decreasing %CV
Reducing the risk of
complications and mortality and
improving patient QoL
Optimise HbA
1c
1,2
<7.0%
Reduce glycaemic
variability
1–4
%CV ≤36%, TIR >70%
4
+ =
總結：國際臨床指引建議 T1DM 和T2DM成人的CV% 和TIR目標

血糖控制不太好，心腎共
病多,近期有ACS,這次抽
血檢查出現蛋白尿加劇，
腎臟功能一年比一年差，
很害怕未來要洗腎 …
•Current treatment
•Metformin+SGLT2i+SU
•Basal Plus, GLP-1RA
•ACEI +CCB+β-blocker
•Crestor(20)
•Plavix
•Status
•HbA1c12.3%
•eGFR 50ml/min/1.73 m
2
•BP 146/83mmHg
•UACR463mg/g
我需要新的治療嗎 ?
•Medical history
•T2DM(27 y/rs)
•Hypertension
•Hyperlipidemia
•DKD(stage3A)
•CAD
•BMI:29.7kg/m
2
68歲
1.ASCVD
2.Indicatorsof high risk:
大多為≥55歲帶有兩項以
下風險因子
(肥胖、高血壓、抽菸、高血脂
或蛋白尿 )
1.Case sharing

6.0%
7.0%
8.0%
9.0%
10.0%
11.0%
12.0%
13.0%
112.03 112.06 112.09 112.12 113.01 113.04
HbA1C
Time
HbA1c變化
Jardiance duo 1#bidPC
Toujeo12uQDHS
Xigduo1# qdPC
Toujeo18uQDHS
Glucovance1# bid PC
Toujeo12uQD
Sema1mg/week HS
Glucovance1# bid PC
Toujeo18uQD
Sema1mg/week HS
Toujeo12uQD
Novorapid(8u, 12u, 12u) TID AC
Forxiga1#qd
Case a few month later…
5/14-5/27
CGM
Toujeo10uQD
Novorapid(8u, 10u, 10u)TID AC
GalvusMet 1#bid
113.07113.04
如何幫助患者達到優質照護指標
HbA1C 12.3 9.2 9.8 7.2 9.0 6.8
AC Sugar 376 146 164 118 143 101
PC Sugar 278 196 226 136 245 134

UACR:463mg/g 248mg/g
使用SGLT2i&GLP-1RA前後UACR& eGFR血糖變化
12months
46%
Regression to UACR <300 mg/g
巨量→ 微量
eGFR:50 58ml/min/1.73m2
12months
16%

14天CGM報告
GMI:7.3TIR:54%CV%:44%

•14天
調
整
作
息
與
習
慣
控
管
與
調
整
醫
囑
成
效
評
估
裝機治療四階段
14天與4期TIR值變化
觀
察
平
常
生
活
型
態
TIR:54% 79%
放任期約束期控管期成果期

14天CGM血糖與胰島素趨勢
Mallya cap & 智抗糖APP

控管成果期（ 5/23/-5/27）

14天CGM血糖與胰島素趨勢控管成果期（ 5/23/-5/27）
（34%→50%)
（29%→56%)

1.Acute stage of illness Insulin BG
2. ASCVD GLP1-RA CV risk
3. CKD, HF SGLT2i UACR eGFR
4. OBESITY GLP1-RA, SGLT2i, 飲食,運動 BW
5. Glycemic Variability CGM, DPP4i TIRCV%
6. Early combination SGLT2i+Met, DPP4i+Met Durability
藥物飲食衛教運動衛教智慧醫療
Thinkingprocess 基本要件

T1DM和T2DMCGM裝機後HbA1C皆呈現改善1
T1DM和T2DMCGM裝機前後兩週 TIR比較第二週皆呈現改善
.
2
T1DMCGM裝機前後兩週 TBRL1:54-69mg/dl比較第二週皆呈現改善3
Gla-300&智慧醫療應用是優化血糖變異性和 TIR有效糖尿病控制的基礎
4TAR和TBR之間的 gap大小與CV%的高低趨勢是一致的
智慧醫療工具輔助
Conclusion

•工欲善其事
•必先利其器
Thanks for Your Attention
工欲善其事必先利其器

1130820-家醫群家醫計畫2.0-實體+線上-社團法人高雄市醫師公會.pdf

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1130820-家醫群家醫計畫2.0-實體+線上-社團法人高雄市醫師公會.pdf

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