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慢性腎臟病與糖尿病藥物

光田綜合醫院 新陳代謝科

曾士婷醫師

2017.5.

1

藥物動力學

2

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全球糖尿病盛行率

Lancet. 2016 Apr 5. pii: S0140-6736(16)00618-8. doi: 10.1016/S0140-6736(16)00618-8.

從1億8百萬到 4億2千2百萬人

人口結構改變39.7%

兩者互動31.8%

盛行率改變 28.5%

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 with

undiagnosed

diabetes (20-79)

in 1,000s

China 10.6 9.8 57 813.6

Hong Kong 10.2 8.0 273.5

Taiwan 10.0 8.4 828.3

Singapore 12.8 10.5 253.8

Japan 7.6 5.7 3 353.8

Korea 8.7 7.2 1559.0

Australia 6.3 5.1 493.9

USA 12.8 10.8 8 284.6

UK 6.2 4.7 1 068.9

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

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5

Chronic Complications of DM

Diabetic

Retinopathy

Leading cause

of blindness

in working age

adults1

Diabetic

Nephropathy

Cardiovascular

Disease

Stroke

2 to 4 fold increase in cardiovascular mortality and stroke3

Diabetic

Neuropathy

Leading cause of

non-traumatic lower

extremity amputations5

8/10 diabetic patients

die from CV events4

1 Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99–S102. 2Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94–S98. 3 Kannel WB, et al. Am Heart J 1990; 120:672–676. 4Gray RP & Yudkin JS. In Textbook of Diabetes 1997.5Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78–S79.

30% of Type 1 Diabetes40% of Type 2 Diabetes

Progression of DN

6The kidney at a glance. 2000; 82-2000 Blackwell Science Ltd.

Hyperfiltration

GBM thickening,Mesengial expansion

020 1015 525Years from diagnosis of diabetes

Stage 2 Microalbuminuria-BP rising

Stage 2 Hypertension

Stage 3 Proteinuria

Stage 4 Rising creatinine

Stage 5 ESRD

Pro

gression

of d

iabetic n

eph

rop

athy

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• Optimize glucose control

• Optimize blood pressure control (<140/90 mmHg)

• Dietary protein intake

–Not dialysis dependent: 0.8 g/kg body weight per

day.

– on dialysis: higher levels of dietary protein intake

should be considered

• ACEI or ARB

RecommendationsDiabetic Kidney Disease

American Diabetes Association Standards of Medical Care in Diabetes. Microvascular

complications and foot care. Diabetes Care 2016; 39 (Suppl. 1): S72-S80

Prevalence of ESRD

per

mil

lion

pop

ula

tion

https://www.usrds.org/2007/view/12_intl.asp

Atlas of End-Stage Renal Disease in the United States

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Diabetes, the Leading Cause of ESRD in Taiwan since 2000

9TSN Renal Registry1990~2001，Nephrology Dialysis Transplantation 23:3977-3982 Yang WC & Hwang SJ, 2008

The Progressive Nature of DN

10J Clin Invest. 2006 Feb;116(2):288-96.

Type 2 DM (20-40%)

GF

R(m

l/m

in)

Time after diagnosis (yr)

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Prediction Probability for Incidence or

Progression of CKD After 5.5 years in

T2DM

11Modified from Clin J Am Soc Nephrol. 2015 Aug 7;10(8):1371-9.

5 2515

For incidence of CKD

UACR (mg/g)

UACR (mg/g)

For progression of CKD

50 100 200

eGFR CKD-EPI eGFR CKD-EPI

Predicted Probabilities for

Death within 5.5 years in T2DM

12

eGFR CKD-EPI eGFR CKD-EPI

For death

For death

UACR (mg/g)

5 15 25

UACR (mg/g)

50 100 200

Modified from Clin J Am Soc Nephrol. 2015 Aug 7;10(8):1371-9.

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Diabetic Nephropathy-DN

–GFR-Glomerular filtration rate

–Proteinuria

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Stages of CKD

Stage Description GFR

(mL/min/1.73M2)

1 Kidney damage

with normal or ↑

GFR

≥ 90

2 Kidney damage

with mild ↓ GFR

60-89

3 Moderate

↓ GFR

30-59

4 Severe ↓ GFR 15-29

5 Kidney failure < 15

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NKF KDOQI GUIDELINES

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Hyperglycemic Damage Pathway

Clinical diabetes, Vivian A. Fonseca, 2006

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Vasopressor peptide

Sympathetic activation

Elevation in blood pressure

Hyperglycemia

Metabolic change Hemodynamic change

Diabetic Nephropathy (DN)

Type 1 DM Type 2 DM

Reactive oxygen species

Inflammatory cytokines

Growth & apopototic factor

17Clinical Diabetes , Vivian A. Fonseca, 2006

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CKD造成血糖異常之各項因素

37 1

CKD造成血糖異常之各項因素

37 1

低血糖 監測困難

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Diabetes and ESKD

• Reducing insulin requirements

• Difficult vascular access

• Accelerated macrovascular disease

• Advanced microvascular disease

• Frequent sepsis

• Silent ischaemia

• 2-3 x death rate vs non-DM patients

Burnt-Out Diabetes

Semin Dial. 2014 March ; 27(2): 135–145. doi:10.1111/sdi.12198. 1

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Burnt-Out Diabetes

• 1.營養不良、糖尿病導致的胃腸消化不良

• 2.因為腎臟對胰島素的清除率下降，導致胰島素作用延長

• 3.因為肝臟對胰島素的清除率下降，導致胰島素作用延長

• 4.因為腎臟萎縮降低腎臟的醣類再生作用

• 5.累積一些毒素例如guanidino compounds ，和biguanide agents 構造相似

22

糖化血色素目標

01/Semin Dial.

2014 March ; 27(2):

135–145.

doi:10.1111/sdi.121

1

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與糖代謝有關的實驗室及臨床數據

• 糖化血色素(A1C)

• 空腹血糖 (AC sugar)

• 餐後血糖 (PC sugar)

• 血漿C-peptide濃度

• 血漿insulin濃度

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A

B

C

建議的血糖控制目標

Adapted from 中華民國糖尿病學會 2006 第2型糖尿病照護指

引p.9.

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口口服抗糖尿病藥物Oral Antidiabetic Drugs (OAD)服

抗糖尿病藥物Oral Antidiabetic Drugs (OAD)

26

01/11/2013 1Nephrol Dial Transplant (2014) 29: 1284–

1300

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口服降血糖藥物的種類

• 胰島素分泌促進劑(insulin secretagogues)

– 磺醯尿素(sulfonylureas)

– Glinides (又稱Meglitinides類似物)

• 胰島素敏感劑 (insulin sensitizer)

– 雙胍類 ( Biguanides)

– Glitazones (Thiazolidinediones, TZD)

• 阿爾發－葡萄糖甘酶抑制劑(α-glucosidase inhibitor )

• 二肽基肽酶抑制劑(DPP-4 Inhibitor)28

Major Targeted Sites of Oral Drug

Classes

29Buse JB et al. In: Williams Textbook of Endocrinology. 10th ed. Philadelphia: WB Saunders; 2003:1427–1483; DeFronzo RA. Ann Intern Med.

1999;131:281–303; Inzucchi SE. JAMA 2002;287:360-372; Porte D et al. Clin Invest Med. 1995;18:247–254.

DPP-4=dipeptidyl peptidase 4; TZDs=thiazolidinediones.

Glucose

absorption

Hepatic glucose

overproduction

Impaired insulin

secretion

Insulin

resistance

Pancreas

↓Glucose level

Muscle

and fatLiver

Biguanides

TZDs Biguanides

TZDs

α-Glucosidase

inhibitors

Gut

Sulfonylureas

Meglitinides

DPP-4 inhibitors

DPP-4 inhibitors

Biguanides

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醫院常見之口服降血糖藥物 (1)

學名 商品名 劑量範圍

(mg/day)

Peak

level

(h)

Half-

life

(h)

代謝途徑

(腎/肝)

健保價

(元)

Sulfonylurea

Glipizide GliDiab 2.5-40 1-3 2-4 80/20 2.18/ 5mg

Gliclazide Mezide 80-320 4–6 10.4 65/25 5/ 80mg

Glibenclamide Gliben 1.25-20 ~4 10 50/50 1.74/ 5mg

Glimepiride Amaryl 1-8 2-3 9 60/40 10.5/ 2mg

Meglitinide

Repaglinide Novonorm 1.5-12 0.75 1 -/100 5.8/ 1mg

D-phenylalanine

derivative

Nateglinide Starlix 360 1.0 1.4 80/10 7.3/

120mg30

醫院常見之口服降血糖藥物 (2)

學名 商品名 劑量範圍

(mg/da

y)

Peak

level

(h)

Half-

life

(h)

代謝途徑

(腎/肝)

健保價

(元)

Biguanide

Metformin Glibudon 750-

2550

1-2 6 90/10 2.35/

500mg

a-glucosidase

Inhibitor

Acarbose Glucobay 75-300 ~ ~ ~ 5.8/ 50mg

Thiazolidinedio

ne

Rosiglitazone Avandia 4-8 1 3-4 ~ 39/ 4mg

Pioglitazone Actos 15-45 2 3-7 20/80 59/ 30mg31

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選擇口服降血糖藥物之考量原則

需依據患者之病情

• 胰島素分泌不足 ( Insulin deficiency) 或胰島素作用不良( Insulin resistance)?

• 血糖之高低與糖尿病症狀之嚴重程度

• 飲食習慣與進食狀況

• 肝、腎、心臟功能與併發之疾病

• 自理生活之能力與居家照顧之品質

• 藥物之療效

• 低血糖等副作用的風險

• 價格因素

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胰島素分泌促進劑

• 磺醯尿素(sulfonylureas)– A1C 降低約1-2%

– 最大降糖效果通常在仿單建議最大劑量的1/2~2/3時便已達到

• Glinides (Meglitinides analogue)– A1C 降低約0.8%

– 作用快速，須隨餐服用，可降低餐後高血糖

– 短效，較少低血糖副作用

– Repaglinide 不可與gemfibrozil 併用

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SU的作用機轉

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Insulin Secretagogues類

01/11/2013 1

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SFU in CKD

• Depends on Renal or Hepatic metabolism

• Depends also on whether metabolites have hypoglycemic effects

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Insulin Sensitizers類

01/11/2013 1

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Metformin

• 常用於過重或肥胖的（準）糖尿病患者

• 並不刺激胰島素分泌，單獨使用少見低血糖副作用

• 抑制肝糖新生與製造，因而降低空腹血糖

• 治療後不會增加體重

• 可改善血脂肪異常，對內皮細胞功能等心血管危險因子有正向的影響

• 常見腸胃道一過性副作用，低劑量起始可避免

• 肝腎心肺功能不良不宜使用，以免發生40

Biguanide(雙胍類)的作用機轉

1. Metformin降低肝臟中

的葡萄糖新生作用

2. 降低或延遲腸道葡萄糖吸收

3. 促進GLUT4移動到細胞表面而增加胰島素敏感性

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Thiazolidinediones

• 活化peroxisome proliferative-activated receptor-γ (PPAR-γ)，而增加胰島素之敏感度，降低空腹血糖及血中胰島素濃度

• 降糖效果較緩慢，通常需6至8週才見成效

• 需在內生或外源性胰島素存在下才有作用

• 可改善內皮細胞功能，發炎指摽等心血管疾患危險因子

• 與metformin 併用對改善胰島素阻抗性有加成作用

• 常見副作用有體重增加、水腫等，需密切追蹤肝指數如ALT，若ALT值超過正常上限的三倍，應停藥

• 重度心臟衰竭者不宜使用

42

43

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44

45

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46

Acarbose

• 抑制近端小腸澱粉及雙醣類之分解，延緩葡萄糖的吸收，降低飯後血糖、胰島素濃度，甚至空腹血糖

• 不被腸胃道吸收(<1%)

• 無體重增加之副作用

• 副作用為輕至中度的脹氣、腹瀉；自低劑量起始可減緩(start low, go slow)

• 低血糖僅出現於合併療法時，須使用葡萄糖或牛奶治療

• 使用於輕中度糖尿病之單一治療或合併治療

• 可減低葡萄糖耐量異常患者轉變為第2型糖尿病的機率及發生心血管疾患的風險 ，減緩頸動脈內膜厚度增加速率 (STOP-NIDDM)

• 可減低第2型糖尿病患者心肌梗塞風險(MeRIA)47

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α-Glucosidase inhibitors類

01/11/2013 1

DPP-4 Inhibitor 二肽基肽酶抑制劑

作用機轉

•抑制DPP-4酵素提昇incretins濃度，包括GLP-1及GIP的濃度。

•incretins是體內平衡葡萄糖生理調節之內因系統一部份，當血糖升高時，GLP-1與GIP會提高胰臟β細胞合成及釋出胰島素作用；GLP-1也會降低α細胞昇糖素分泌作用，進而降低肝臟葡萄糖生成

副作用

•對照性臨床研究中，不論單一或合併療法，表現出良好耐受性，出現臨床不良反應而停藥者與安慰劑相當

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DPP-4 Inhibitor 二肽基肽酶抑制劑:提升活性incretin濃度

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*Refers to amino acid number.

Deacon CF et al. Diabetes. 1995;44:1126–1131.

Meal

Intestinal

GIP and GLP-1

release

GIP and GLP-1

Actions

DPP-4

Enzyme

GIP-(1-42*)

GLP-1(7-36)*

Intact (active)

GIP-(3-42)*

GLP-1(9-36)*

metabolites

Rapid InactivationX

DPP-4

Inhibitor

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Incretin-Based Insulin Secrtagogues類

01/11/2013 1

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Nephrol Dial

Transplant (2014)

29: 1284–1300

1

低血糖副作用及策略• 危險因子

– 老年、營養狀況不佳、餐無定時、或合併有肝腎功能異常者

• 低劑量起始

• 高危險族群考慮使用glinide

• 腎功能不良者考慮短效、具不活性代謝物、由肝臟排除者尤佳，可使用glinide

• 餐無定時或常誤餐者，可使用glinide

• 注意藥物交互作用– Alcohol, anticoagulant, trimethoprim

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• 抗糖尿病藥物胰島素

•

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何時需使用胰島素?• 第1型糖尿病患者

• 第2型糖尿病患者– 空腹血糖超過300 毫克/毫升 和合併酮體血症或酮體尿

症。

– 持續性出現空腹血糖超過 300 毫克/毫升 和出現多尿、多喝、及體重減輕的症狀

• 糖尿病酮酸血症患者

• 肝腎功能不良的糖尿病患者

• 因急性病症住院的糖尿病或高血糖患者

• 口服抗糖尿病藥物療效不佳者

• 願意接受胰島素做為第一線治療的患者

• 妊娠性糖尿病患者無法以飲食控制者

• 糖尿病婦女懷孕時59

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Insulin in pt. on hemodialysis

•Insulin inhibitors – dialyzable

•Insulin resistance diminishes after the start of dialysis.

•half-life of insulin is prolonged.

•the potential for hypoglycemia with both oral agents and insulin increases in the presence of CKD (with the exception of gliquidone and glimepiride).

•Self-monitoring of blood glucose concentration is imperative.

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正常人血糖與胰島素濃度曲線

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Continuous basal insulin secretion

Incremental prandial insulin secretion

Starting Dose

1 x Basal 10 IU (bedtime)

FBG value in millimoles per liter

0.16 IU/Kg

1 x Premix 10 IU ( Presupper)

2 x Premix 10 IU ( Prebreakfast), 10 IU ( Presupper)

MDI Individualized

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Scheme for Adding Basal or Intermediate-Acting Insulin to Oral Agents

64

Start with 5–10 units; increase by 2–3 units every 3 days

until FPG is between 110 and 120 mg/dl

Clinic- vs. Patient-driven Titration of Basal Insulin

--AT.LANTUS Study

24

140 and <180 mg/dl

(7.8 and <10 mmol/l)

Increase in daily basal insulin glargine dose (U)

26–8

180 mg/dl

(10 mmol/l)

22120 and <140 mg/dl

(6.7 and <7.8 mmol/l)

0–20–2100 and <120 mg/dl

(5.5 and <6.7 mmol/l)

Algorithm 2:

Patient-driven titration

every 3 days

Algorithm 1:

Clinic-driven titration

at every visit

Mean FBG for the

previous

3 consecutive days

Davies M et al. Diabetes Care2005;28:1282–8

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Self-Titration of Insulin Detemir:

The PREDICTIVE 303 Study• 303 Algorithm Sites: Patients to adjust dose every 3 days based on mean FPG values

• Standard-of-Care sites: Physician to adjust dose based on standard-of-careMeneghini et al. Diabetes Obes Metab. 2007;

9:902-13

FPG (mg/dL) Basal Dose Adjustment

< 80 Reduce detemir dose by 3U

80-110 No change

>110 Increase detemir dose by 3U

Key Learning Points

• There are clinical advantages of pens over vial-and-syringe dosing1,2

• You may need to consider features, advantages, and disadvantages of insulin pens as well as patient needs when selecting an insulin pen

• There are unique features in the insulin pens demonstrated today that may help you individualise care for your patients

1. Summers KH, et al. Clin Ther. 2004;26(9):1498-1505. 2. Cobden D, et al. Pharmacotherapy. 2007;27(7):948-962.

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Clinical advantages of pens over vial-and-syringe dosing

Ease of use2

Social acceptability2

Lifestyle adaptability2

Why Use an Insulin Pen?

•Patients with diabetes may benefit from modern insulin injection pens that provide an accurate way to inject insulin.1

1. Hänel H, et al. J Diabetes Sci Technol. 2008;2(3):478-481. 2. Summers KH, et al. Clin Ther. 2004;26(9):1498-505. 3. Cobden D, et al.

Pharmacotherapy. 2007;27(7):948-962.

Reduced risk for

hypoglycaemic events3

Overall reduced healthcare

costs3

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Why Use an Insulin Pen? (continued)

Insulin pens:

Accurate dosing1-

4

Flexible2,3,5,6

Convenient2,3,5,6

1. Shelmet J, et al. Diabet Res Clin Pract. 2004;63(1):27-35. 2. Hänel H, et al. J Diabetes Sci Technol. 2008;2(3):478-481. 3. Korytkowski M, et

al. Clin Ther. 2005;27(Suppl B):S89-S100. 4. Lombardo F, et al. Acta Biomed. 2005;76(S3):S66-S69. 5. Korytkowski M, et al. Clin Ther.

2003;25(11):2836-2848. 6. Bohannon NJ, et al. Clin Ther. 2000;22(9):1049-1067. 7. Fox C, et al. Practical Diabetes International.

2002;19(4):104-107.

Discreet2,4,5,6

Easy to use1-7

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Humalog KwikPen

•Humalog KwikPen is an easy-to-use, easy-to-inject pre-filled pen1

•For patients who want a portable device

•For patients desiring discreet insulin delivery

1. Data on file, Lilly USA, LLC; KwikPen Design Validation User Study. HUM20071024A.

Select Safety Information:

Pens and needles are for single-patient use only and should not be

shared, even in healthcare facilities, as infection or disease can be

spread from one person to another.

Do not withdraw insulin from the pen.

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Humalog KwikPen (continued)

• Humalog KwikPen has the following advantages:

• Easy to set the dose

• Easy to see numbers

• Easy to dispense maximum dose of 60 units*

• Easy to dispense dose*

*Humalog KwikPen Design Validation User Study included adult male and female participants with type 1 and type 2 diabetes. Of the total 150 study

participants, 56 were insulin-naïve, 42 were currently administering insulin with a vial and syringe, and 52 were experienced insulin pen users.

Data on file, Lilly USA, LLC; KwikPen Design Validation User Study. HUM20071024A.

Easy to dial up and back down for

dose correction

Short thumb-reach at high doses

Small, lightweight, and portable

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KwikPen® 讓使用胰島素變得更容易

1. Ignaut et al. Diabet Educ 2009;35(5):789-98.

‧好學好用 ‧喜好度高 ‧重量輕 1 1

喜好度分數1

Overall satisfaction

Easy to UseVial & Syringe

Humalog KwikPen

Easy to Learn

Percentage of respondents

Use in work,school orpublic setting

0 20 40 60 80 100

92.2

91.8

90.9

89.1

10.9

9.1

8.2

7.8

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Laboratory Evaluation of Humalog® KwikPenTM vs FlexPen®: Study Design

Ergonomic and glide force injection measurements were

evaluated for a new prefilled insulin pen (Humalog KwikPen)

and compared to the currently available prefilled insulin pen

(FlexPen)

Humalog KwikPen containing Humalog® Mix75/25™

(75% insulin lispro protamine suspension and 25%

insulin lispro injection)1,2

FlexPen containing NovoLog® Mix 70/30 (70% insulin

aspart protamine suspension and 30% insulin aspart)3

1Ignaut DA et al. J Diabetes Sci Technol 2008;2(3):533-5372http://www.humalog.com/patient/humalog_kwikpen.jsp3http://www.novonordisk.com/about_us/history/milestones_in_nn_history.asp

® Humalog and Humalog KwikPen are registered trademarks of Eli

Lilly and Company® FlexPen is a registered trademark of Novo Nordisk A/S

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Humalog KwikPen (A)

FlexPen (B)

Overall Length (in) 5.69 6.23

Weight w/ cap (g) 31.12 23.98

Diameter across cartridge holder (in)

0.56 0.51

Data from Ignaut DA et al. J Diabetes Sci Technol 2008;2(3):533-537® Humalog and Humalog KwikPen are registered trademarks of Eli Lilly and Company ® FlexPen is a registered trademark of Novo Nordisk A/S

Laboratory Evaluation of Humalog® KwikPenTM vs FlexPen®

Ergonomic Testing Results

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Distance (in) Humalog KwikPen (A)

FlexPen (B)

At 30 units 0.95 1.20

At 60 units 1.50 1.83

Data from Ignaut DA et al. J Diabetes Sci Technol 2008;2(3):533-537® Humalog and Humalog KwikPen are registered trademarks of Eli Lilly and Company ® FlexPen is a registered trademark of Novo Nordisk A/S

Laboratory Evaluation of Humalog® KwikPenTM vs FlexPen®

“Thumb Reach” Distances

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Humalog KwikPen FlexPen

Ignaut DA et al. J Diabetes Sci Technol 2008;2(3):533-537® Humalog and Humalog KwikPen are registered trademarks of Eli Lilly and Company ® FlexPen is a registered trademark of Novo Nordisk A/S

Laboratory Evaluation of Humalog® KwikPenTM vs FlexPen®

“Thumb Reach” Dialed Out to 60 Units

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Laboratory Evaluation of Humalog® KwikPenTM vs FlexPen®

Injection Force Characteristics

30-Unit Dose 60-Unit Dose

Humalog KwikPen

FlexPen Humalog KwikPen

FlexPen

Maximum Glide Force (lbs)

3.42 ± 0.35 5.36 ± 0.76 3.61 ± 0.40 5.62 ± 0.77

Average Glide Force (lbs)

3.31 ± 0.35 4.95 ± 0.65 3.39 ± 0.38 5.08 ± 0.66

Glide Force Variability at Plateau Curve (lbs)

0.30 ± 0.06 0.76 ± 0.32 0.57 ± 0.15 1.01 ± 0.42

Data represent the mean ± standard deviation;

All treatment comparisons were statistically significant, P<0.0001

Data from Ignaut DA et al. J Diabetes Sci Technol 2008;2(3):533-537® Humalog and Humalog KwikPen are registered trademarks of Eli Lilly and Company ® FlexPen is a registered trademark of Novo Nordisk A/S

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30 Units

Time (s)

0 1 2 3 4 5 6

Gli

de

Fo

rce (

lbs

)

0

2

4

6

8

10

Time (s)

0 1 2 3 4 5 6

KwikPen

FlexPen

60 Units

Abbreviation: s, seconds. Data from Ignaut DA et al. J Diabetes Sci Technol 2008;2(3):533-537® Humalog and Humalog KwikPen are registered trademarks of Eli Lilly and Company ® FlexPen is a registered trademark of Novo Nordisk A/S

Laboratory Evaluation of Humalog® KwikPenTM vs FlexPen® Glide Force Profile

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FlexPen

● Lighter in weight

● Smaller in diameter at the cartridge holder

Humalog KwikPen

● Shorter in overall length

● Shorter “thumb reach”

● Requires less effort to inject

● Provides smoother and more consistent delivery

Ignaut DA et al. J Diabetes Sci Technol 2008;2(3):533-537® Humalog and Humalog KwikPen are registered trademarks of Eli Lilly and Company ® FlexPen is a registered trademark of Novo Nordisk A/S

Laboratory Evaluation of Humalog® KwikPenTM vs FlexPen® Key Results Summary

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Primary Objective: Response to the Final Preference Question (FPQ)

Humalog KwikPen vs NovoLog® FlexPen®

Patient Preference

n=76

n=155

0

20

40

60

80

100

FPQ

Pe

rce

nta

ge

of

Re

sp

on

de

nts

NovoLogFlexPen

HumalogKwikPen

Ignaut DA, et al. Diabet Educ. 2009;35(5):789-798.

Which Insulin Pen Would You Prefer?

80

Humalog KwikPen vs NovoLog FlexPen

• Secondary Objective

• To what extent do you agree that the pen just assessed has these features?

• Overall ease of use1

• Ease of holding in hand when injecting1

• Ease of pressing injection button when injecting dose1,2

1. Ignaut DA, et al. Diabet Educ. 2009;35(5):789-798. 2. Ignaut DA, et al. J Diabetes Sci Technol. 2008;2(3):533-537.

Adapted from J Diabetes Sci Technol, 2008.2

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Humalog KwikPen vs NovoLog FlexPenPen Use Scores

n=38n=13

n=46 n=39

n=147

n=179

0

20

40

60

80

100

NovoLog FlexPen Humalog KwikPenPe

rce

nta

ge

of

Re

sp

on

de

nts

Was the Pen Overall Easy to Use?

Other

Agree

Strongly Agree

P=.006 Humalog KwikPen vs FlexPen for users who either agreed or strongly agreed.

*IDAB Question 14.Ignaut DA, et al. Diabet Educ. 2009;35(5):789-798.

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Humalog KwikPen vs NovoLog FlexPenPen Use Scores (continued)

n=62 n=29

n=48 n=49

n=122

n=153

0

20

40

60

80

100

NovoLog FlexPen Humalog KwikPenPe

rce

nta

ge

of R

esp

on

de

nts

Was the Pen Easy to Hold in Your Hand When You Injected?

Other

Agree

Strongly Agree

P=.002 Humalog KwikPen vs FlexPen for users who either agreed or strongly agreed.

*IDAB Question 4.Ignaut DA, et al. Diabet Educ. 2009;35(5):789-798.

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Humalog KwikPen vs NovoLog FlexPenPen Use Scores (continued)

n=78

n=34n=48 n=47

n=106

n=150

0

20

40

60

80

100

NovoLog FlexPen Humalog KwikPen

Pe

rce

nta

ge

of

Re

sp

on

de

nts

Was It Easy to Press theInjection Button?

Other

Agree

Strongly Agree

P<.001 Humalog KwikPen vs FlexPen for users who either agreed or strongly agreed.

*IDAB Question 5.Ignaut DA, et al. Diabet Educ. 2009;35(5):789-798.

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