糖尿病的臨床照護與藥物治療klpa.taiwan-pharma.org.tw/sites/klpa.taiwan-pharma.org... ·...

糖尿病的臨床照護與藥物治療

基隆長庚紀念醫院內分泌暨新陳代謝科

陳志宏醫師2017-07-09

糖尿病的臨床照護

糖尿病的診斷與分類

糖尿病的預防

糖尿病的生活方式管理 (Lifestyle Management)

糖尿病的藥物治療 (Pharmacologic Approach to

Glycemic Treatment)

糖尿病的慢性併發症防治

糖尿病的特殊族群照護

* 提醒您: 糖尿病治療藥物的部份, 加入演講者的個人看法, 僅供參酌 !

For training purposes only.

Dulaglutide has received positive opinion from the CHMP; however, there is no guarantee it will receive regulatory approval and become

commercially available in your affiliate.

Diabetes: A Global Emergency

IDF Diabetes Atlas I Seventh edition IAtlas, IDF Diabetes. “7th." International Diabetes Federation (2015).




Prevalence of Diabetes in East Asian Countries Compared

to the United States and Europe: Estimates for 2015

Country

Diabetes

prevalence in 2015

(%)

Diabetes

comparative

prevalence in 2015

(%)

Adults

undiagnosed

diabetes

79)

China 10.6 9.8 57

Hong Kong 10.2 8.0

Taiwan 10.0 8.4

Singapore 12.8 10.5

Japan 7.6 5.7

Korea 8.7 7.2

Australia 6.3 5.1

USA 12.8 10.8

UK 6.2 4.7

Atlas, IDF Diabetes. “7th." International Diabetes Federation (2015).

What percentage of patients globally fail to achieve glycaemic control ?

From a global Type 2 diabetes population of around 377 million…1

71% have high BP5

85% are overweight4

40–70%fail to achieve HbA1c <7.0%2,3

+-

Patients with Type 2 diabetes have

an almost two-fold greater risk of

CVD than those without diabetes6

BP, blood pressure; CVD, cardiovascular disease; LDL, low-density lipoprotein.1. International Diabetes Federation. Diabetes Atlas, 7th edition 2015. Available at: https://www.idf.org/diabetesatlas. Last accessed August 2016; 2. Gakidou E, et al. Bull World Health

Organ 2011;89:172–83;

3. de Pablos-Velasco P, et al. Clin Endocrinol (Oxf) 2014;80:47–56; 4. CDC. Available at: http://www.cdc.gov/diabetes/statistics/comp/fig7_overweight.htm. Last accessed September

2015; 5. CDC. National Diabetes Statistics Report, 2014. Available at: http://www.cdc.gov/diabetes/data/statistics/2014StatisticsReport.html. Last accessed September 2015; 6. Gregg EW,

et al. N Engl J Med 2014;370:1514–23.

Additional risk factors

65% have high blood LDL cholesterol5




More than 56% T2DM Patients are Overweight in Taiwan

56% T2DM

patients

are

overweigh

t*

Yu Neng-Chun, et al., diabetes research and clinical practice 99 ( 2013 )

112 – 119

*BNHP=Bureau of National Health Promotion 國民健康局; WHO definition: Overweight (BMI≥25), Obese(BMI≥30)




UKPDS: Correlation between HbA1c Levels and Adverse

Cardiovascular Events

Menon, Venu, and Bhuvnesh Aggarwal. "Why are we doing cardiovascular outcome trials

in type 2 diabetes?." Cleveland Clinic journal of medicine 81.11 (2014): 665-671.

HbA1c

1%

↑ 14% risk in

fatal and

nonfatal MI

↑ 12% risk in

fatal and nonfatal

stoke

↑ 43% risk in amputations or

deaths from peripheral

vascular disease

↑ 16% risk in

heart failure

糖尿病治療的生活方式管理

(Lifestyle Management) **團隊治療**

營養治療 Diet Control 處方 ( BMI, 工作, 飲食習慣)

* 照會營養師

1) 份量控制 : 五大類食物 (醣類代換)

* 每日總熱量 (Kcal) 份數/餐

2) 均衡飲食 : 多樣化飲食型態(地中海飲食. 得舒飲食 DASH)

3) 健康食物選擇 : 交通號誌分類法, 外食, 節慶飲食* 體重控制

4) 特殊狀況調整 : 生病日, 腎病變, 心衰竭



營養治療 Diet Control 處方** 三大營養素分配個別化衛教CHO: Fat: Protein = 45~55% : 25~35% : 15~25%

** 糖尿病營養品 (早餐. 點心. 生病日)

** 斷食療法 (X) 斷糖飲食 (X) 代餐包 (O)

** 非營養的甜味劑 (O, 應限量, 不鼓勵)

體力活動 Exercise 處方 (評估病況 : retinopathy,

neuropathy, IHD, Stroke 以及體能狀況)

擬訂可行方案 (每周3次，每次30分，流汗 = 60分)

* 照會護理衛教師 (運動教練)

日常生活: 多活動避免久坐每30分鐘起身活動

(= 100分)

每週至少進行150分鐘中等強度以上有氧運動

阻力運動 (重量訓練) 每週進行2~3次但是不要連續

老年糖尿病人每週進行2~3次柔軟度和平衡訓練

運動中的能量代謝

運動強度: 最大攝氧量 = 心跳反應

* 代謝當量 (MET) = 消耗熱量

1代謝當量 = 1 Kcal/Kg/hr = 3.5 mLO2/Kg/min

= 成年人休息時的代謝當量定義為 1 MET

低強度活動: < 3 MET

中強度活動: 3~6 MET

高強度活動: > 6 MET

** 以MET來代表運動強度或能量消耗量 !


舉例說明:

太極拳的代謝當量是4 (= 4 Mets) 一位體重60公斤的人打太極拳30分鐘, 其所消耗的熱量為 60(公斤) X 0.5(小時) X 4 (代謝當量, 1大卡/公斤/小時) = 120 大卡

人體在進行不同的身體活動(包括運動)所消耗的熱量, 會依據體格大小(體重), 運動時間(小時), 運動強度(Met)而有所不同


** 適度運動建議應是中強度 (3-6 MET)

** 只要運動程度能使每分鐘的心跳提升20-40下(比起休息時的心跳) 就能促進健康 !

** 運動程度能達到微喘.流汗 ! (有點累; 可說話, 但無法唱歌)

8 km/hr

9-

10-

11

12

14

16

持續規律運動表

第一步驟：開始運動試著增加一些較緩和的活動來開始，您可以選擇油漆房子、散步、烹飪、燙衣、玩樂器等

第二步驟：輕度活動當您覺得可以再增加運動量時，就可以試著做一些輕度活動，如慢走(4公里/小時)、園藝、打掃房子、照顧小孩、打高爾夫球、乒乓球

第三步驟：中度活動這時你可以試著快走(6.4公里/小時)、騎腳踏車、滑雪、網球、跳舞

第四步驟：重度活動您可以試著進行再加快速度的快走(10公里/小時)活動、負重上坡、玩籃球或足球、爬山、游泳

逐步增強運動能力: 頻率 > 時間 > 強度



衛教計畫** Acute & Chronic Complications (糖尿病併發症衛教)

** 定期檢查的重要性:

眼底檢查 (轉介眼科), 足病變檢查, 微量蛋白尿篩檢EKG, CXR, DM foot 的防治

** 藥物使用方法及副作用“Hypoglycemia”

遵囑性對糖尿病治療的重要性 !!

* 照會藥師或護理衛教師

** 鼓勵糖尿病人參加全民健保糖尿病醫療給付改善方案

Diabetes

The leading cause of new cases of end-stagerenal disease

A 2- to 4-fold increase in cardiovascular risk

The leading cause of new cases of blindness in working-aged adults

The leading cause of nontraumatic lower extremity amputations

Harris MI. In: Diabetes in America. 2nd ed. 1995. Washington, DC: National Institutes of Health; 1995. NIH publication

95-1468. Wingard DL et al. In: Diabetes in America. 2nd ed. 1995. NIH publication 95-1468. Kuller LH. In: Diabetes in

America. 2nd ed. 1995. NIH publication 95-1468.

Clinical Impact of Diabetes Mellitus

• History/physical exam

• Refer once per year to an

ophthalmologist for a

dilated

eye exam

• In-office screening can

be conducted with a

Fundus camera and

photos read by a central

office (EyeTel, Inoveon,

Nidek)

Screening and Diagnosis for Diabetic Retinopathy

Fong DS, et al. Diabetes Care. 2003;26(suppl 1):S99-S102.

Gibbins RL, et al. Diabetologia. 1998;41:59-64.

Images: Ahttp://www.mdmercy.com/news/archives/0102retina_camera.htmlBhttp://www.inoveon.com/index.html

Chttp://www.nidek.com/fundus.html

Screening and Diagnosis

for Diabetic Peripheral Neuropathy

Tuning Fork

Monofilamentscreening test

• History/physical exam

• Eliminate causes other than DPN

• Neurological exam

• Vibration detection threshold (VDT)

• Tuning fork

• Proprioception

• Position sensitivity by

flexion/extension

of great and small toe

• Deep tendon reflexes

• Reflex hammer

• Pressure sensation

• Monofilament

• Pain sensation

• Pin prick

• Light touch sensation

• Cotton-wool swab

• Diagnosis

• Can be supported by:

• Electrophysiology

• Quantitative sensory testing

足部任ㄧ檢查點出現異常即表示有神經病變,

有導致足部潰瘍的危險

• In type 1 diabetes, screening for albuminuria should

begin with puberty and after 5 years’ disease duration

• In type 2 diabetes, screen starting at diagnosis

Screening for Microalbuminuria

Definition: Using microalbumin/creatinine ratio:

30-300 µg/mg

If negative

Rescreen

annually

If positive, repeat in 3-6 mos.

Are 2 of 3 tests

positive?

No

Initiate treatment Yes

CAD-EM-08001

“Adherence is ‘the sixth vital sign’ as important as respiration, heart rate, temperature, blood pressure, and pain (Blood Sugar : 5th vital sign).”

— Dr. Edward C. Rosenow III, Mayo Clinic of Medicine

CAD-EM-08005

Definitions

Adherence: The extent to which a person’s

behavior corresponds with agreed recommendations from a healthcare provider; also called compliance

Persistence: The duration of treatment (ie, the length of time a patient fills his/her prescriptions)

Benner JS et al. JAMA. 2002;288:255-261.

Insull W. J Intern Med. 1997;241:317-325.

World Health Organization. World Health Organization; Geneva, Switzerland. 2003.

CAD-EM-08005

PDC

Proportion of Day Covered

PDC ≥ 80% = Well adherent

Example:

− 180(實際服藥日數)/365(應服藥日數)=49.3%

− 292(實際服藥日數)/365(應服藥日數)=80%

CAD-EM-08005

Insull W. J Intern Med. 1997;241:317-325.

Rudd P. Cardiol Rev. 1994;2:230-240.

Categories of Adherence/Compliance

Category/gradeAdherence (% of time)

CharacteristicsPatients in

category (%)

Compliant ≥80Steady-state pharmacokinetics

50-60

Partially Compliant 20-79Inconsistent dosing

30-40

Noncompliant <20

Patient resists the idea or logistics of treatment

5-10

CAD-EM-08005

Compliance With Therapy Was Less Than Optimal

80%

20%

Patients achieving ≥80% adherence

Patients achieving <80% adherence

Monane M et al. Am J Hypertens. 1997;10:697-704.

Retrospective analysis of claims data from the New Jersey Medicaid and Medicare Programs (N=8643).Compliance was defined by the proportion of days a patient had medication on hand, based on the length of the prescription.

CAD-EM-08005Cheng JWM et al. Pharmacotherapy. 2001;21:828-841.

Patient Reasons for Nonadherence

4%

1%

1%

2%

3%

6%

7%

7%

14%

55%

Don’t think it’s necessary all the time

Hate taking

Don’t like being dependent

Drugs give me side effects

Don’t think drugs are working

Too expensive

Don’t like being told what to take

Just forget

Other

Supply will last longer

Prospective, open-label, interview-based study in metropolitan New York area pharmacies (N=821).

CAD-EM-08005

Avorn J et al. JAMA. 1998;279:1458-1462.

Choice of Medication May Influence Persistence

Cohort study in the New Jersey Medicaid and Pharmacy Assistance for the Aged and Disabled Programs (N=5611) and Quebec’s Provincial Medical Care program (N=1676).

CAD-EM-08005Data on file. Pfizer Inc., New York, NY.

Number of Concurrent Medications Influenced Adherence

0.00

0.50

1.00

1.50

2.00

2.50

3.00

0 1 2 3-5 6+

Number of other prescription medications

Ad

here

nc

e ≥

80

% (

OR

)

P<.0001

P<.0001

P<.0001P<.0002

Retrospective cohort study in a large managed care population (N=8406).

每提升10%的服藥遵醫囑性，可有效降低 A1C 0.1 ~ 0.15%

Pladevall M, et al. 2004, Diabetes Care. Rozenfeld Y, et al. Am J Manag Care. 2008;14:71-5

A 10% increase in index adherence for oral glucose-lowering agents was

associated with a 0.1% decrease in HbA1c (P=0.0004)

4.0

Ad

jus

ted

Hb

A1c

0

4.8

6.0

8.0

7.2

8.8

10 20 40 60 80 90 100

8.4

7.6

6.8

6.4

5.6

5.2

4.4 n=235

705030

Concordance (%)

服藥遵醫囑性

持續衛教工作逐次完成衛教課程 [記錄]

• 營養衛教 • 糖尿病衛教

醣類代換(“量”的觀念) 認識糖尿病生病日注意事項

均衡飲食 (五大類食物) 認識治療藥物認識慢性合併症

體重控制 (交通號誌法) 低血糖教育足部照護

外食、節慶、生病日高血糖急症運動旅行

(腎病變、懷孕、哺乳) 自我監測 (血糖、血酮檢查)

糖尿病患者的追蹤治療計劃: **團隊治療**

1. for Glycemic control

A) Oral agents：

Sulfonylureas:

1 Chlorpropamide (Diabinese)

2 Glyburide (Euglucon, GlucoMet)

Glipizide (Glidiab)

Gliclazide (Diamicron MR)

3 Glimepiride (Amaryl, Amaryl-M)

Biguanide:

Metformin (Glucophage)

-Glucosidase Inhibitor:

Acarbose (Glucobay)

Miglitol

糖尿病治療的藥物選擇


A) Oral agents：

Thiazolidinediones :

Troglitazone ()

Rosiglitazone (Avandia)

Pioglitazone (Actos, AcotosMet)

Glinides:

Repaglinide (Novonorm)

Nateglinide (Starlix)

Mitiglinide (Glufast)



A) Oral agents：

DPP-4 Inhibitors:

Sitagliptin (Januvia, JanuMet)

Vidagliptin (Galvus, GluvesMet)

Alogliptin

Saxagliptin (Onglyza, Combiglyze)

Linagliptin (Trajenta, TrajentaDuo)

SGLT2:

Empagliflozin (Jardiance)

Dapagliflozin (Forxiga)

Canaglifolzin


SGLT2i 0.5-0.9% ++ ++ 低減輕




Meta-analysis: HbA1c Reductions with Antihyperglycemic Agents Added to

Metformina

NNPTW-VIC-PPT02-MYM-10-2016 Date




Metabolic Syndrome is Strongly Associated with Increase

in Abdominal Obesity

Adapted from BMJ 2001.322:716-720

Deterioration Lipid profile Improvement

Impaired Insulin sensitivity Improved

▲ Blood Insulin ▼

▲ Blood Glucose ▼

▲Risk markers for

thrombosis▼

▲ Inflammatory markets ▼

Impaired Endothelial function Improved

Abdominal

Obesity

Increased

waist

circumference

After weight

loss

Reduced waist

circumferenceCV RiskIncreased Low




Weight Loss Provides Multiple Benefits in T2DM patients

AHEAD, Action for Health Diabetes; CI, confidence interval; CVD, cardiovascular disease;

DBP, diastolic blood pressure; HDL, high-density lipoprotein, SBP, systolic blood pressure.

Wing RG, et al. Diabetes Care 2011;34:1481–6.

Odds ratio meaningful changes in CVD risk factors at 1 year after a weight loss of

≥5% to <10% (n=1000/5145)

This study was an observational analysis of participants in the Look AHEAD study conducted at 16 US sites in 5,145

participants (40.5% male, 37% from ethnic/racial minorities).

Clinical criteria Odds ratio 95% CI

0.5% in HbA1c 3.52 2.81, 4.40

5 mmHg in SBP 1.56 1.27, 1.91

5 mmHg in DBP 1.48 1.20, 1.82

5 mg/dL in HDL cholesterol 1.69 1.37, 2.07

40 mg/dL in triglycerides 2.20 1.71, 2.83




Look AHEAD: Incidence of Cardiovascular Disease Varied

by Changes in Weight (overall study population)

Lancet Diabetes Endocrinol. 2016 Nov;4(11):913-921.

• Lost at least 10% of

their body weight in the

first year of the study

• 21% lower risk of the

primary outcome

• 24% reduced risk of the

secondary outcome.




What Do Patients Think was Most Important

1. Avoiding weight increase

2. Achieving weight loss

3. Reducing the risk of hypoglycaemia

4. Reduce HbA1c

44SEK: Swedish Krona (kr)

Jendle J. et al. Curr Med Res Opin. 2010 Apr;26(4)917-23.

Willingness-to-pay for beneficial attributes

Amount needed to accept the change

①

②

④

③

A comparison of WTP values for different realistic

changes in levels of attributes showed that weight

gain and loss (>2 kg) were the most important

aspects of diabetes treatment, together with a

reduction in hypoglycaemic events from two per

month to none and a HbA1c reduction of 1

percentage point (Figure 1).

405.920,022_FOR_29/06/2015

Weight change following newly diagnosed type

2 diabetes and risk of cardiovascular mortality

CVD death All cause death

Weight Gain 1.63 (1.11–2.39) 1.34 (1.01–1.76)

Unchanged 1.00 Reference 1.00 Reference

Weight loss 1.06 (0.76–1.48) 1.06 (0.85–1.33)No. events 197 423

Similar to Look

AHEAD study

results

New

finding

Diabetes Metab. 2013 Sep;39(4):306-13. Presented EASD in October 2012

Adjusted for age, gender, BMI at baseline, previous angina pectoris, education, marital status and glucose lowering drugs.

47

Difference in change from baseline in body weight, kg (95% CI)

Weight neutral

Weight gain

Weight loss

Treatment

Sulphonylureas

Meglitinides

Thiazolidinediones

DPP-4 inhibitors

α-glucosidase inhibitors

GLP-1 analogues

Basal insulin

Biphasic insulin

2.01 (1.09–2.94)

1.80 (0.35– 3.29)

2.59 (1.66–3.51)

0.57 (-0.45–1.60)

-0.92 (-2.35–0.51)

-1.79 (-3.43– -0.14)

1.56 (-0.46–3.63)

2.96 (0.96–5.00)

Adopted from McIntosh B, et al. Open Medicine 2011;5(1):e35

Weight gain is a common side effect of T2DM medications

48

• Each additional tolerability issue is associated with a 28% greater likelihood of medication non-adherence5

• Symptoms of hypoglycaemia: non-adherence by 76%• Constipation/diarrhoea: non-adherence by 47%

Metformin1,2 Gastrointestinal disturbance, lactic acidosis

Sulphonylureas1,2 Hypoglycaemia, weight gain

Thiazolidinediones1,2 Weight gain, oedema, congestive heart failure

Meglitinides2 Hypoglycaemia, weight gain

-glucosidase inhibitors1,2 Gastrointestinal disturbance

GLP-1 mimetics3 Gastrointestinal disturbance

SGLT2 inhibitors4 Increased urinary volume, urinary tract and genital infections, AEs related to volume depletion

Insulin1 Hypoglycaemia, weight gain

AE=adverse event

1. Adopted from Moller D. Nature 2001;414:821–7; 2. Adopted from Inzucchi SE. JAMA 2002;287:360–72;

3. Adopted from Garber AJ. Diabetes Care 2011;34 (Supplement 2):S279–84;

4. Adopted from Fujita Y, Inagaki N. J Diabetes Investig 2014;5(3):265–75; 5. Adopted from Pollack MF, et al. Diab

Res Clin Prac 2010;87:204–10

Tolerability issues associated with antidiabetic medications contribute to increased non-adherence

Metformin

優點: 改善胰島素抗性 (esp. liver) Uncertain mechanism

Low risk of hypoglycemia ** PCOS

Weight Reduction

Long term safety profiles

Potential anti-aging and anti-cancer effects

預防糖尿病 (pre-DM) *便宜

缺點: * Vitamin B12 deficiency [應定期追蹤檢測]

High frequency of GI side effects (需由低劑量使用)

Rare incidence of lactic acidosis

Contra-indications: elderly, severe major organ failure

Sulfonylurea (SU) & Glinide

優點: 刺激胰島素分泌快速改善血糖控制

降醣效果佳

Sulfonylurea Qd (服用方便) *便宜 (SU)

缺點: 刺激胰島素分泌高胰島素血症

High risk of hypoglycemia

Weight gain

Poor glycemic durability (SU)

Potential CAD risk (loss of ischemic preconditioning)

Glinide Tid (服用不便; 但藥效較短, 比起SU安全些)

KATP Channel Complex

Some sulfonylureas are

not selective for heart or

pancreas KATP channels

SFU SUR2A

Kir6.2Responsible

for K+ flux

SFU SUR1

Kir6.2

68% homology

The KATP channel, a complex of a sulfonylurea receptor (SUR2A, SUR1) and the potassium

channel (Kir6.2) is key to glucose-mediated insulin release from pancreatic -cells

Ischemic Preconditioning (IP)

IP is a powerful, endogenous mechanism by which the heart protects itself from lethal ischemic insult

IP occurs when cardiac KATP channels open automatically during brief episodes of mild myocardial ischemia

Drugs that inhibit cardiac KATP channel opening may be harmful to the ischemic myocardium by blunting the KATP

channel-dependent component of the ischemic preconditioning response

Brady et al. J Am Coll Cardiol 1998;31(5):950.

55

Risk of hypoglycemia with different sulfonylureas

*<50 mg/dL.

Tayek J. Diabetes Obes Metab. 2008; 10: 1128–1130.

Slide Source:

Lipids Online Slide Librarywww.lipidsonline.org

160

150

140

130

120

ADOPT: A Diabetes Outcome Progression Trial

Reprinted with permission from Kahn SE et al. N Engl J Med. 2006;355:2427-2443.

Copyright © 2006 Massachusetts Medical Society. All rights reserved.

0

1

Fasting P

lasm

a G

lucose

(mg/d

l)

Time (years)

0 1 2 3 4 5

Rosiglitazone Sustained Fasting Plasma Glucose Over Time

0

3408 3054 2647 2242 840Number of patients: 4118

SU

MET

RSG

Treatment Difference at 4 Years

RSG VS MET -9.8 (-12.7 to -7.0), P<.001

RSG VS SU -17.4 (-20.4 to -14.5), P<.001

TZD (Glitazone) - Actos

優點: 改善胰島素抗性 (esp. muscle) Unique mechanism

Low risk of hypoglycemia

Glycemic durability

CV safety and protection

缺點: *昂貴

CHF, 10-20% edema

Weight gain

Bone fracture, a significant risk for females especially post-menopausal

Bladder cancer, increased relative risk, but rare

How to Minimize the Side Effects of PPAR-γ Agonists ?

Use lower doses

Avoid using in combination with insulin in high-risk patients

Avoid use in patients with high risk for fractures

Decrease salt and calorie intake

Avoid calcium channel blockers

Discontinue if patients have weight gain and edema

-Glucosidase Inhibitor (AGI)

優點:


Good weight profile

Good lipid profiles

Incretin effect

Effects on microbiota ?

Potential anti-cancer or ant-ageing effects ?

缺點:

Major side effects: GI

Tid (服用不便; CHO-intake較少者, 效果較差)

Acarbose* acts non-systemically†,1

to delay carbohydrate digestion and

absorption

62

* Lifestyle intervention is the first and basic component in the management of diabetes. † The bioavailability of acarbose is 1-2%.1. Summary of product characteristics (2012). Available at http:// www.medicines.org.uk.2. Figure modified from Standl E, et al. Diab Vasc Dis Res 2012;9:163-9.

Upper small

intestine

Lower small

intestine

Without

acarbose

Carbohydrate

absorption

Carbohydrates

With

acarbose

Carbohydrate

absorption

● Effect of Glucobay on GIP and GLP-1 (healthy subjects)

Mixed Meal

Subjects: 14 healthy subjects Method: Subjects were randomized to receive Glucobay at 100 mg or no Glucobay in order to

measure blood GLP-1 etc. after ingestion of mixed meal.

Am J Physiol Gastrointest Liver Physiol 281:752-763, 2001.

● With Glucobay

● Without Glucobay

0 20 40 60 90 120 150 180 (min)

10

30

50

70

90

110

130

GIP

(pm

ol/L

)

＊

++

++

++

++

++

34

0 20 40 60 90 120 150 180 (min)

14

18

22

26

30＊

＊＊

＊

GLP

-1(p

mol/L)

* P<0.01 (comparison between groups)

++ P<0.001 (comparison between groups)

Glucobay decreases GIP secretion and

increases GLP-1 secretion

64

* cox proportional hazards model:

time to single OGTT > 11.1 or < 7.8 mmol/L: acarbose vs placebo

Reduction in incidence of

type 2 diabetes* (p = 0.0015)

29.5 %

24. 8 %

Increase in incidence of

normal glucose homeostasis*

(p <0.0001)

STOP-NIDDM : Acarbose Progression / Regression of Disease in IGT, not in DM

65

CV Risk Reduction on Acarbose

91 % p= 0.0226*Myocardial Infarction

34 % p= 0.0059*New Hypertension

49 % p= 0.0326*

Chiasson et al. Diabetologia 2002; 45, Suppl. 2: A104

Any CV-Event

Chiasson et al. Diabetologia 2002; 45, Suppl. 2: A104

DPP-4 Inhibitors

優點:


Weight neutral

Good safety profiles

CV outcome neutral [but Saxagliptin (Alogliptin) CHF]

Glycemic durability

Qd (多數藥物, 服用方便)

缺點: *昂貴

需隨腎功能變化而調整藥物劑量 (除Linaglipin外)

GLP-1 life cycle

Smits, Mark M., et al. "GLP-1 based therapies: clinical implications for gastroenterologists." Gut (2016): gutjnl-2015.

Food

intake

Stomach

GI tract

Intestine

α-cells

Pancreas

Glucose-dependant

insulin secretion

-cellsDPP-4

inhibitor

Glucagon secretion

Incretins

DPP-4 inhibitors enhance incretins activity

DPP-4

Incretins (腸泌素) 作用機轉

Adapted from: 1. Drucker DJ, Nauck MA. Lancet. 2006;368:1696-705.

2. Idris I, Donnelly R. Diabetes Obes Metab. 2007;9:153-65. 3. Barnett A. Int J Clin Pract. 2006;60:1454-70.

Increases and prolongs

GLP-1 effect on α-cells

Increases and prolongs GLP-1and GIP effects on β-cells

Net effect:

blood glucose

GLP-1 RA

69

TW1212069167

Differentiation of DPP-4 inhibitors

70

TW1212069167

Reference:. Diabetes Metab. 2012 Oct;38(4):359-66. doi: 10.1016/j.diabet.2012.06.001. Epub 2012 Jul 17.

Clinical Therapeutics/Volume 34, Number 6, 2012

Overall mean changes from baseline in HbA1c and FPG

DPP-4 inhibitors: dose adjustment in CRI

5mg5mg

5 m

g

10

0 m

g

5 m

g

50

mg

25 m

g

50

mg

BID

50 m

g Q

D

2.5

mg

Linagliptin

(Trajenta®)

Sitagliptin

(Januvia®)Vildagliptin

(Galvus®)

Saxagliptin

(Onglyza®)

No renal

issues

At risk of renal

impairment

Mild renal

impairment

Moderate renal

impairment

Severe renal

impairment

SGLT2i

優點: Low risk of hypoglycemia

Weight Reduction

Good CV outcome (esp. CHF)

Glycemic durability

Qd (服用方便)

缺點: *最昂貴

腎功能惡化時藥效變差(Gapagliflozin: eGFR < 60, Empagliflozin: eGFR < 45 不可處方)

Genital infection, UTI; Volume depletion; DKA (AKI, Bone fracture ?, Lower limb amputation ?)

• SGLT2 inhibitors (SGLT2-Is) can reduce renal glucose reabsorption and allow excess

glucose to be excreted in urine

Lee YJ et al. Kidney Int Suppl 2007; (106):S27-35.

Hummel CS et al. Am J Physiol Cell Physiol 2011; 300:C14-21.

Proximal tubule

Glucose filtration

SGLT1 accounts for

~10%of renal glucose

reabsorption

SGLT2 INHIBITORS

Reduced glucose

reabsorption

Increased urinary

excretion of excess

glucose (~70 g/day,

corresponding to 280

kcal/day*)

Action of SGLT2 Inhibitors




Evidence for use across a broad range of treatments:

Consistent HbA1c reductions over a number of combinations

*Statistically significant versus placebo (p<0.0001); †Statistically significant versus placebo (p<0.001).

FORXIGA has not been studied in combination with GLP-1 analogues.

DPP4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1; OAD, oral antidiabetic drug; SU, sulphonylurea.

1. Ferrannini E, et al. Diabetes Care 2010;33:2217–24; 2. Bailey CJ, et al. Lancet 2010;375:2223–33; 3. Strojek K, et al. Diabetes Obes Metab 2011;13:928–38; 4.

Mathieu C, et al. Presented at the Annual Scientific Sessions of the American Diabetes Association, Boston, USA. 5–9 June 2015. Abstract 105-OR;

5. Wilding JPH, et al. Ann Intern Med 2012;156:405–15; 6. Matthaei S, et al. Poster presented at the 49th European Association for the Study of Diabetes, Barcelona,

Spain. 23–27 September 2013; Abstract 937-P.

Ad

just

ed

me

an

ch

an

ge

fro

m b

ase

lin

e H

bA

1c

at

24

w

ee

ks

(%)

Add-on to a SU3

Add-on to metformin2

Monotherapy1

Add-on to insulin ±OADs5

Add-on to a DPP4 inhibitor ±metformin4

Add-on to metformin +

SU6

FORXIGAPlacebo

8.24% 8.16%8.07% 8.15%7.92% 8.11%7.84% 8.57% 8.47% 8.1% 8.2%Mean baseline HbA1c 8.01%

EMPA-REG MONO: Change in HbA1c at Week 24 in patients with baseline HbA1c ≥ 8.5%

77

CI, confidence interval; HbA1c, glycosylated haemoglobin; QD, once daily. *p < 0.05 vs sitagliptin;

**p < 0.01 vs sitagliptin; ****p < 0.0001 vs placebo. ANCOVA (LOCF). Reprinted from Roden M, et al. Lancet Diabetes

Endocrinol. 2013;1(3):208–219, with permission from Elsevier

Adju

ste

d m

ean (

95%

CI)

change

fro

m b

ase

line

in H

bA

1c

(%)

Baseline mean

9.06 9.16 9.18 8.99

****

*****

******

Placebo

(n = 51)

10 mg

(n = 54)

25 mg

(n = 45)

Sitagliptin

(n = 51)

JARDIANCE®

p < 0.05 vs sitagliptin; p < 0.01 vs sitagliptin

EMPA-REG MONO/MET/METSU (open-label): Change in HbA1c at Week 24 in patients with baseline HbA1c ≥ 10.0

78

BL, baseline; HbA1c, glycosylated haemoglobin; QD, once daily; SE, standard error; SU, sulphonylurea.

1. Roden M, et al. Lancet Diabetes Endocrinol. 2013;1(3):208–219;

2. Häring H-U, et al. Diabetes Care. 2014 (in press);

3. Häring H-U, et al. Diabetes Care. 2013;36:3396–404.

Mean (SE)

adjusted

change from

baseline in

HbA1c (%)

-3.70 (0.21)

0

N/Week BL 6 12 18 24

Monotherapy 87 77 74 73 66

Add-on to metformin 69 66 60 58 48

Add-on to metformin + SU 101 94 89 77 70

-3.23 (0.22)

-2.89 (0.16)

JARDIANCE® reduced FPG (mg/dL) across different background therapy compared with placebo*

79

Phase III pooled efficacy analysis

Patients, n 831 821 224 224 217 213 165 168 225 216 169 155 98 97

BL FPG (mg/dL) 152.6 152.

6

152.8 152.6 154.59 149.37 151.9 151.7 150.84 156.42 138.0 146.0 145.8 147.6

BL, baseline; FPG, fasting plasma glucose; MET, metformin; PIO, pioglitazone; QD, once daily;

RI, renal impairment; SE, standard error; SU, sulphonylurea. * All data are placebo-corrected and statistically significant unless otherwise marked.

1. Hach T, et al. Diabetes. 2013;62(suppl 1A);A21 (P69-LB); 2. Roden M, et al. Lancet Diabetes Endocrinol. 2013;1(3):208–219; 3. Häring H-U, et al. Diabetes Care. 2014 (in press);

4. Kovacs C, et al. Diabetes Obes Metab. 2014;16(2):147–158; 5. Häring H-U, et al. Diabetes Care. 2013;36(11):3396–404; 6. Rosenstock J, et al.

Diabetologia. 2013;56(suppl 1);S372 (P931); 7. Barnett A, et al, Lancet Diabetes

Endocrinol. 2014; doi:10.1016/S2213-8587(13)70208-0.

Pooled data JARDIANCE® 10 mg QD JARDIANCE® 25 mg QD

Monotherapy MET PIO MET+SUPooled Mild RIInsulin

78 week

Ad

juste

d m

ea

n (

SE

) d

iffe

rence v

s

pla

ce

bo

in

ch

an

ge

fro

m b

ase

line

in

FP

G (

mg

/dL

)

EMPA-REG RENAL: Change in HbA1c in patients with renal impairment (Stage 2 CKD)

80

Ad

juste

d m

ea

n (

95

% C

I) c

ha

ng

e

fro

m b

ase

line

in H

bA

1c

(%)

****

****

CI, confidence interval; CKD, chronic kidney disease

(Stage 2 = eGFR ≥ 60 and < 90 mL/min/1.73 m2; eGFR, estimated glomerular filtration rate; HbA1c, glycosylated haemoglobin; QD, once daily.

****p < 0.0001 vs placebo. ANCOVA. FAS (LOCF). Barnett A, et al. Lancet Diabetes

Endocrinol. 2014;doi:10.1016/S2213-8587(13)70208-0.

Placebo

(n = 95)

10 mg QD

(n = 98)25 mg QD

(n = 97)

Mean baseline HbA1c (%)

8.09 8.02 7.96

JARDIANCE®

JARDIANCE® should not be initiated in patients with an eGFR < 45 mL/min/1.73 m2

Evidence for use across a broad range of treatments: Additional benefit of weight loss over a number of combinations

FORXIGA is not indicated for the management of weight loss. Weight change was a secondary endpoint in clinical trials.

*Statistically significant versus placebo (p<0.0001).

FORXIGA has not been studied in combination with GLP-1 analogues.

DPP4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1; OAD, oral antidiabetic drug; SU, sulphonylurea.

1. Ferrannini E, et al. Diabetes Care 2010;33:2217–24; 2. Bailey CJ, et al. Lancet 2010;375:2223–33; 3. Strojek K, et al. Diabetes Obes Metab 2011;13:928–38; 4. Mathieu C, et

al. Presented at the Annual Scientific Sessions of the American Diabetes Association, Boston, USA. 5–9 June 2015. Abstract 105-OR;

5. Wilding JPH, et al. Ann Intern Med 2012;156:405–15; 6. Matthaei S, et al. Poster presented at the 49th European Association for the Study of Diabetes, Barcelona, Spain. 23–

27 September 2013; Abstract 937-P.

Ad

just

ed

me

an

ch

an

ge

fro

m b

ase

lin

e

we

igh

t a

t 2

4 w

ee

ks

(kg

)

Add-on to a SU3

Add-on to metformin2

Monotherapy1

Add-on to insulin ±OADs5

Add-on to a DPP4 inhibitor ±metformin4

Add-on to metformin +

SU6

Ad

just

ed

me

an

ch

an

ge

fro

m b

ase

lin

e b

od

y w

eig

ht

at

24

we

ek

s (k

g)

FORXIGAPlacebo

91.0 89.380.56 80.9486.3 87.794.2 88.8 94.5 94.5 88.6 90.1Mean baseline weight (kg)




Dapagliflozin demonstrated a significant reduction in fat mass rather than lean tissue or fluid loss sustained up to 102 weeks

Bolinder J, et al. Diabetes Obes Metab 2014;16:159–69J, et al. Lancet

Weight Loss Mainly Associated with

Body Fat Mass Reduction




Reduction in waist circumference (cm) from baseline

in placebo, Dapa 5mg and Dapa 10mg at week 24

Significant Waist Circumference Reduction

in Asian Patients as Add-on to Metformin

Wais

t cir

cum

fere

nce

(cm

)

Yang, Wenying, et al. Journal of diabetes (2015). doi: 10.1111/1753-0407.12357

3-point MACE

84

Empagliflozin 10 mgHR 0.85

(95% CI 0.72, 1.01)p=0.0668


(95% CI 0.73, 1.02)p=0.0865

Cumulative incidence function. MACE, Major Adverse Cardiovascular Event; HR, hazard ratio

All-cause mortality

85

HR 0.68

(95% CI 0.57, 0.82)

p<0.0001


(95% CI 0.56, 0.87)p=0.0013


(95% CI 0.54, 0.83)p=0.0003

Kaplan-Meier estimate. HR, hazard ratio

Hospitalisation for heart failure

86


(95% CI 0.45, 0.86)p=0.0044


(95% CI 0.50, 0.93)p=0.0166

Cumulative incidence function. HR, hazard ratio

Incident or worsening nephropathy

in patients with prevalent kidney disease*

HR 0.58(95% CI 0.47, 0.71)

p<0.001

Cu

mu

lative

pro

ba

bili

ty o

f e

ve

nt

(%)

*Defined as eGFR (MDRD) <60 mL/min/1.73m2 and/or macroalbuminuria (urine albumin-to-creatinine ratio >300 mg/g) at baseline.

Kaplan-Meier estimates in patients with prevalent kidney disease treated with ≥1 dose of study drug.

Hazard ratios are based on Cox regression analyses. Post-hoc analyses.

eGFR, estimated glomerular filtration rate. MDRD, Modification of Diet in Renal Disease.

“Safety update information. Product is not approved for renal risk reduction.”

AstraZeneca do not recommend the use of Forxiga in any manner other than T2DM

The potential effects of SGLT2 inhibitors on

several CV risk factors

CV, cardiovascular; TG, triglyceridesInzucchi SE, et al. Diab Vasc Dis Res 2015;12:90–100

Reductions in blood pressure

Improved endothelial function and reduce

arterial stiffness

Small increases in HDL-cholesterol and

reduced TG

Reductions in urinary albumin

excretion

Reductions in uric acid

Weight loss and reduced visceral fat The potential

effects of SGLT2 inhibitors on CV risk

factors include:

88

Overview of SGLT2i CV Outcome Trial

Ref: https://clinicaltrials.gov/

EMPA-REG CANVAS + CANVAS-R DECLARE

n 7020 4330 5811 17,150

Interventions EMPA 10 mg

EMPA 25 mgPlacebo 1:1:1

CANA 100 mg

CANA 300 mgPlacebo 1:1:1

CANA 100 or

300 mgPlacebo 1:1

DAPA 10 mgPlacebo 1:1

Inclusion criteria T2DM, ≥18 y/o

A1c 7-10%

Established CV

disease

(MI, CAD, UA, stroke,

PAD)

T2DM

A1c 7-10.5%

≥30 y/o with history of CV events or

≥50 y/o with ≥ 2 risk factors for CV

disease (DM≥10 years, SBP≥140

mmHg with anti-HTN drugs, smoking,

albuminuria, HDL<1 mmol/L [39 mg/dl])

T2DM, ≥40 y/o

A1C 6.5-12%

Established CV diseases (MI, CAD,

stroke, TIA, PAD) or

≥ 2 risk factors for CV disease

(age>55 years in men, >60 in women; dyslipidemia, HTN, tobacco use)

Primary endpoint CV death, non-fatal MI, non-fatal stroke

CV death, non-fatal MI, non-fatal stroke

Progression of

albuminuria

CV death, non-fatal MI, non-fatal

ischemic stroke; CV death +

Hospitalization for HF

(Estimated) follow-up median 3.1 years median 6 years 3.5 years median 4.5 years

Study completion date April 2015 February 2017 April 2019

Estimated reporting Sep. 2015 Jun.12th , 2017 ADA Apr. 2019

https://clinicaltrials.gov/

Study findings: Change in HbA1c and body weight in the all-patient cohort

Wilding et al. Poster presented at Diabetes UK (DUK) conference 2017. Manchester, UK

HbA1c, glycated hemoglobin

Change in weight (kg) and HbA1c (%) at 181–365 days

(n = 1331)

Change in HbA1c (%)

Ch

an

ge

in

we

igh

t(k

g)

10.7% 1.8%

13.0%70.2%

N.B. Data are for patients who had a measurement of HbA1c AND weight within the time frame.

Decreases in HbA1c correlated with decreases in weight in the all-patient cohort

459.511,022_FOR_02/05/2017

= 12.5% 體重不減

= 14.8% 血糖不降

Meta-analysis of SGLT2i-related

genitourinary infections

Treatment for SGLT2i-related genitourinary infections

94

• Bacterial lower UTI (urethritis/cystitis):oral TMP/SMZ or 2G cephem for 3 days

• Candidal balanoposthitis:topical cream treatment (ex. Sertaconazole, Fenticonazole)

• Vulvovaginal candidiasis:topical cream treatment, intravaginal suppository (ex. Sertaconazole, Fenticonazole, Nystatin), or single dose fluconazole 150 mg

459.511,022_FOR_02/05/2017

Sliding toward euglycemic DKA

Diabetes Care 2015;38:1638–1642

Precipitating Factors Leading to DKA

DKA = diabetic ketoacidosis; LADA = latent autoimmune diabetes in adults; SGLT2 = sodium-glucose cotransporter- 2; T1D = type 1 diabetes

mellitus.

1.Umpierrez GE, Kitabchi AE. Treat Endocrinol. 2003;2(2):95-108.

2.Kitabchi AE, et al. Diabetes Care. 2009; 32(7):1335-1343.

3.Rosenstock J et al. Diabetes Care. 2015;38:1638-1642.

General1,2

• Discontinuation of or inadequate insulin therapy

• Infection

• Intercurrent illness• Surgery

• Trauma

• Myocardial infarction

• Pancreatitis

• Physiological stress

• Drugs that affect carbohydrate metabolism

• Cerebrovascular accident

Factors seen with SGLT2i use3

• Infection, surgery, or intercurrent illness

• Discontinuation of or inadequate insulin therapy• Patients with marked ß -cell

insufficiency

• Patients with LADA with rapid evolution toward T1D and during prolonged starvation

• Reduced food and fluid intake

• History of alcohol intake

96



B) Injection agents

(1) GLP-1 RA：1. GLP-1 RA 種類：短效 Exenatide (Byetta 5, 10) Bid

Lixisenatide Qd

中效 Liraglutide (Victoza 0.6, 1.2, 1.8) Qd

長效 Duraglutide (Trulicity 0.75, 1.5) Qw

Bydureon, Albiglutide, Semaglutide

2. GLP-1 RA 處方： Bid Qd , Qhs Qw

Combined therapy (+ OADs , + Basal insulin 限Victoza)

* 護理衛教師: 協助教導及查核針劑的注射技術和使用劑量,以及衛教低血糖防治 (*胰島素治療)




Classification of currently available GLP-1 RAs

by structure and duration of action

Waldrop, G. et al. J Am Coll Cardiol. 2016; 67(12):1488–96.

GSK

Semaglutide

Novo Nordisk

Glucose-Lowering Effect of DPP-4i and GLP-1RA

Waldrop, Greer, et al. "Incretin-Based Therapy for Diabetes: What a Cardiologist Needs to Know." Journal of the American College of Cardiology67.12 (2016): 1488-1496.

GLP-1 RA開源 vs. DPP-4i 節流

• GLP-1 RA 提供較DPP-4i 更高濃度的GLP-1，可帶給患者多重益處

Madsbad et al. Lancet 2009;373:438–9

Dose-Response Relation for GLP-1 Effects

Pancreas

Stomach

Heart

Brain

Liver

Adapted from Baggio & Drucker. Gastroenterol 2007;132;2131–57

Intestine

Cardioprotection

Cardiac function

Satiety

Learning and neuroprotection

(animal studies & Phase 2 clinical trails)

Gastricemptying

Glucose production

Glucose-dependentinsulin secretion

Insulin synthesis

Glucose-dependentglucagon secretion

β

GLP-1: an incretin hormone with multiple direct effects on human physiology

β

β

α

α

GLP-1

L-cells secrete GLP-1 degraded by DPP-4

Primary and Exploratory Outcomes

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER)

Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med


Hazard ratio (95% CI) p-value

Liraglutide Placebo

N % N %

Number of patients 0.027 4668 100.0 4672 100.0

eGFR >60 0.94 (0.83 ; 1.07) 436 12.3 471 13.0

eGFR 30–59 0.67 (0.54 ; 0.83) 147 14.7 197 21.1

eGFR ≤30 0.89 (0.51 ; 1.54) 25 21.4 26 24.3

Primary outcome:Sensitivity analysis by baseline renal status

Post-hoc analysis.CI, confidence interval; eGFR, estimated glomerular filtration rate.Marso SP,et al. N Engl J Med. 2016 Jul 28;375(4):311-22

Hazard ratio (95% CI)

Favours PlaceboFavours Liraglutide

10 .2 2

106

Complementary features of basal insulin and GLP-1 receptor agonists

Balena, R., et al. "Combination therapy with GLP‐1 receptor agonists and basal insulin: a systematic review of the literature." Diabetes, Obesity and

Metabolism15.6 (2013): 485-502.

2017 ADA Guideline of Diabetic Treatment

•Pharmacological Therapy for Type 2 Diabetes:

•Combination Injectable Therapy

•Basal insulin plus GLP-1 receptor agonists are associated with less hypoglycemia and weight loss, but may be less tolerable and have a greater cost.

• In November 2016, the FDA approved two different once-daily combination products containing basal insulin plus a GLP-1 receptor agonist: insulin glargine plus lixisenatide and insulin degludec plus liraglutide.

Nauck et al. Diabetes Care 2009;32;84–90 (LEAD-2; change in body weight by weight loss quartile)

Increasing body weight loss

Change in b

ody w

eig

ht

(kg)

The 25% of subjects who lost most weight lost a mean of 7.7 kg

-7.7

-3.7

-1.8

+1.3

Q1 Q4Q3Q2

Liraglutide 1.8 mg + metformin

Q1: mean weight change for the 25% of subjects who had the smallest weight lossQ2: mean weight change for the 25% of subjects who had >25–≤50% weight loss Q3: mean weight change for the 25% of subjects who had >50–≤75% weight loss Q4: mean weight change for the 25% of subjects who had the largest weight loss



B) Injection agents

(2) Insulin：1. Insulin 種類：超短效(速效) (Lispro, Aspart, Apidra)

短效 (RI)

中效 (NPH)

長效 (Glargine [Gla-300], Detemir,

Degludec)

預混型 (Novomix 50/50, 70/30; Humalog 50/50, 75/25)

Premixed vs. Patient-mixed

2. Insulin 處方： Qd , Qhs ; Bid ; Tid ; Tid + Q hs

Combined therapy (+ OADs , + GLP-1 RA)

CSII (insulin Pump)

Implantable intraperitoneal insulin infusion pump

ADA-EASD Position Statement: Management of

Hyperglycemia in T2DM

Long (Detemir)

Rapid (Lispro, Aspart, Glulisine)

Hours

Long (Glargine)

0 2 4 6 8 10 12 14 16 18 20 22 24

Short (Regular)

Hours after injection

Insu

lin le

vel

Therapeutic options : Insulin

Intermediate (NPH)

Insulin apidra

50/50 aspart insulin

Gla-300

116

WHEN BASAL INSULIN

DOSE OVER 0.5U/KG,

THE A1C LOWERING

EFFECT WILL

DECREASE

L Monnier, C Colette, Diabetes Metab 2006;32:7-13

Figure 2

Relationship between insulin doses (unit/kg of body

weight/day) and weight gain (upper part of the figure).

Relationship between insulin doses (unit/kg of body

weight/day) and decrements in HbA1c (lower part of the

figure). (Isosceles triangles = ref 21; right angle triangles

= ref 22; squares = ref 24; rhombuses = ref 25; crosses =

ref 26; circles = ref 27; black figures are shown for

addition of insulin glargine; open figures are shown for

addition of NPH insulin or rapid-acting insulin analogue).

0.5 U/kg

Optimization of insulin therapy in patients with Type 2 diabetes mellitus: beyond basal insulin.Blak, B; Smith, H; Hards, M; Curtis, B; Ivanyi, T

Diabetic Medicine. 29(7):e13-e20, July 2012.DOI: 10.1111/j.1464-5491.2012.03586.x

1/4

OADs + Basal insulin therapy




QD BID TID QID

Pre-mix BIDBasal

Pre-Mix BID 的另一選擇 :Humalog Mix50 與 Humalog Mix25 合併使用

Humalog Mix 25 Bid / Mix25+Mix50

Humalog Mix 50 Bid / Mix50+Mix25

120

可以依據病人的血糖變化而組合不同的胰島素劑型

Which insulin regimen is the best for diabetic patient ?

@ 降血糖能力: (學理上及臨床研究)

Basal-bolus >= Premixed bid-tid = Basal-plus > BOT

@ Real-world : 加入Compliance (Adherence)的影響降血糖能力會有所改變 !

@ 方便性 : Basal insulin + OADs (BOT)

Premixed > Basal-bolus & Basal-plus

@ 安全性 : Basal-bolus, BOT > Premixed, Basal-plus

與糖尿病人及家屬會談共同研商, 找出最佳的方案 !

Which insulin regimen is the best for diabetic patient ?

@ Type 1 diabetes:Basal-Bolus = 三餐飯前速效 + 睡前長效 [治療首選]

Insulin Pump (CSII) [自費選項]

Premixed Insulin Bid ~ Tid [較不被推薦]

@ Type 2 diabetes:BOT = Basal insulin + OADs [治療首選]

BOT + Victoza (肥胖或過重的糖尿病人的優先選項)

** Premixed insulin Bid Tid 或是** Basal-Plus Basal-Bolus 則是最後不得以的選擇

** OADs 特別是 metformin 應該儘量持續合併處方(除非是體重過輕的患者), 另外可加入 DPP-4i

(體重正常患者) 或是 SGLT2i (肥胖或過重的患者)


•2017 ADA Guideline of Diabetic Treatment

• Pharmacological Therapy for Type 2 Diabetes:

• In patient with long-standing suboptimally controlled type 2 diabetes and established atherosclerotic cardiovascular disease, empagliflozin or liraglutide should be considered as they have been shown to reduce cardiovascular and all-cause mortality when added to standard care.

• Renal effects may also be considered when selecting glucose-lowering medications for individual patients

• Drug choice is based on patient preferences !

Thank You

糖尿病的臨床照護與藥物治療klpa.taiwan-pharma.org.tw/sites/klpa.taiwan-pharma.org... ·...

Documents