1 2013 11

2013 11

CONTENTS ........ 1 Special Issue . 3 ... 7 ........ 8 .......... 8

Victoza pen. ( )

1.

2.

Liraglutide 6mg/ml ( 3ml)

3. :

4. GLP1(Glucagon-like peptide-1) receptor agonist

5.

2

6.

: 1 1 0.6mg,

1 1.2mg

: 1.8mg

7.

Peak : 8~12

: 13L

: 24

: 13

: urine (6%), feces (5%)

8.

: , , , , ,

,

: ,

: ,

: antiliraglutide

:

9.

1

10.

: FDA category C

:

11.

(30C) 1

1 1 , ,

.

.

, ,

, .

, , .

30 .

2 2013 11

(GLP-1 analogue)

(Victoza pen.) (Byetta pen.)

Liraglutide Exenatide

1ml , Liraglutide 6.0mg 1.2ml , exenatide 0.3

2.4ml , exenatide 0.6

3ml / PEN 1.2ml / PEN, 2.4ml / PEN

/ Novo nordisk

/ ()

Bristol-Myers Squibb

/,

GLP1(Glucagon-like peptide-1) receptor agonist

2

1.

2.

3.

1 1

0.6mg 1 1

1 , 1.2mg 1 1

( 1.8mg)

1 1 2 , 60

1 5mcg

1 10 mcg

(1.2ml/PEN: 1 5mcg, 60 dose,

2.4ml/PEN: 1 10mcg, 60 dose)

PK

Peak : 8-12hr

: 13L

: 24hr

: 13hr

: urine (6%), feces (5%)

Peak : 2hr

: 28.3L

: 2.4hr

: urine

( 3.6-

27.4%), (28%), (11%), (17%),

(10%), (6%), (9%), (5%)

Anti-liraglutide antibody,

( 14-36%),

(44%), (13%), (13%), (

3 2013 11

Special Issue

Incretin Based Therapies

1. (incretin)?

1)

2) GLP-1 (Glucagon like peptide-1) GIP (Glucose-dependent insulinotropic

polypeptide)

3) , DPP(Dipeptidyl peptidase)-

4 2

4) (Incretin effect) :

5) GIP GLP-1

GIP

(Glucose-dependent insulinotropic polypeptide) GLP-1

(Glucagon like peptide-1)

5~7 1~2

K cell in duodenum, jejunum L cell in ileum & colon

, , , , , ,

-, , , , ,

2. 2

1)

) 3

(uptake)

Incretin Effect Incretin Effect Incretin Effect

4 2013 11

) 'Ominous Octet' (8 )

) 3

(incretin)

2)

: 8

3. Incretin Based therapies

1) :

,

2) : ,

3) GLP-1 (Glucagon-like peptide-1) receptor agonists

Exenatide(Twice daily, Once weekly), Liraglutide (Once daily)

: , cell ,

: 2

4) DPP-4 (Dipeptidyl peptidase-4) inhibitors

Sitagliptin(Januvia), Vildagliptin(Galvus), Linagliptin(Trajenta), Saxagliptin(Onglyza)

: DPP-4 GLP-1 GLP-1

, ,

: 2

5 2013 11

[]

Sitagliptin

(Januvia)

Saxagliptin

(Onglyza)

Linagliptin

(Trajenta)

Vildagliptin

(Galvus) Twice-Daily Exenatide Liraglutide

Once-Weekly

Exenatide

Dosage 100 mg/day 2.5-5 mg/day 5 mg/day 50 mg bid 5 mcg bid for 1

monthly; then 10 mcg bid if tolerated

0.6 mg/day; increase weekly as tolerated up

to 1.8 mg/day 2 mg once weekly

Dosage adjustment with kidney

impairment

CrCl 30-49 : 50 mg/day CrCl < 30

: 25 mg/day

CrCl 50

: 2.5 mg/day

Adjustment

not needed

Adjustment not

needed

Adjustment not needed, but use

caution if CrCl is 30-50, and avoid if < 30

Adjustment not needed

Use with caution in patients with kidney

impairment

Same as for twice-

daily formation

Primary glycemic focus Postprandial Postprandial Postprandial Postprandial Postprandial Postprandial Fasting and Postprandial

Adverse effect profile Upper respiratory tract infection, urinary tract infection, headache,

hypoglycemia (when taken with sulfonylurea), angioedema (rare), case reports of acute kidney failure and pancreatitis

Nausea, vomiting, constipation, diarrhea, hypoglycemia, case reports of acute kidney

failure and pancreatitis

Injection site pruritus, nausea,

vomiting, diarrhea

Comparative efficacy*

Monotherapy

vs.

placebo -0.79% -0.63 to 0.65% -0.69% -1.0% -0.7 to 0.9% -1.65% NS

metformin 0.145%-0.51% 0.24%-0.30% NS 0.4% NS NS -0.05%

pioglitazone 0.48% NS NS (rosiglitazone)0.2% NS NS 0.10%

GLP-1 agonist 0.38% NS NS NS NA NA NA

DPP-4 inhibitor NA NA NA NA NS NS -0.38%

sulfonylurea NS NS NS 0.1% NS -0.81% NS

+ Metformin

vs.

placebo -0.65% -0.82% -0.64% to

0.73% -0.35% -0.60% to 0.86% -1.1% NS

sulfonylurea 0.035%-0.07% 0.06% NS 0.0% NS 0.0% NS

thiazolinedione 0.06% NS NS -0.11% NS NS -0.3%

DPP-4 inhibitor NA NA NA NA NS -0.9% -0.6%

GLP-I agonist 0.9% NS NS NS NA NA NA

*Efficacy denoted as between group difference in A1C change from baseline (positive difference suggests the comparator medication more effective).

Bid = twice daily; CrCl = creatinine clearance (mL/min); DPP-4 = dipeptidyl peptidase-4; GLP-1 = glucagon-like peptide 1; NA = not applicable; NS = not studied.

Ref. PSAP 2013 New Pharmacotherapies for Type 2 Diabetes

Profile of vildagliptin in type 2 diabetes: efficacy, safety, and patient acceptability. Therapeutics and Clinical Risk Management 2013:9 247-257

6 2013 11

4. Upcoming incretin-based therapies by manufacturer and stage of development

Name (brand name) Developer Remarks

GLP-1 receptor agonists

Albiglutide (Syncria) GlaxoSmithKline p; GLP-1 dimer fused to human albumin; once weekly

Lixisenatide (Lysumia) Sanofi/Zealand Pharma p; In vitro binds to human GLP-1R with greater affinity

than native human GLP-1; Once daily

Dulaglutide Eli Lilly p; GLP-1 analogue fused to Fc antibody fragment; Once

weekly

Exenatide-QM Amylin Pharmaceuticals p; Once monthly

ITCA 650 Eli Lilly/ Intarcia

Therapeutics

p; Exenatide administered using a DUROS device; Once

yearly

Semaglutide Novo Nordisk Unique acylated human GLP-1 with a half-life of 160h

allowing once weekly dosing; Once weekly

DPP-4 Inhibitors

Alogliptin (Nesina) Takeda p; approved for use in Japan

Gemigliptin (Gemiglo) LG life Sciences, Korea p; approved for use in Korea

Dutogliptin Phenomix p

Melogliptin Glenmark p

Teneligliptin Mitsubushi Tanabe p

Gosogliptin Pfizer p

Carmegliptin F Hoffman-La Roche p

Evogliptin Dong-A ST, Korea p

p: Phase I, p : phase , p: phase

Reference

1. , . Incretin-based Combination Therapy in Type 2 Diabetes Mellitus. J Korean Med Assoc 2009;

52(10):1030-1036

2. . Incretin . Korean Diabetes Journal June 2009 Vo. 33 Supplement 3

3. 2 , 2013

4. Susan L. Samson and Alan Garber. GLP-1R agonist therapy for diabetes: benefits and potential risks. Curr Opin

Endocrinol Diabetes Obes 2013, 20:87-97

5. Ralph A. DeFronzo. From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2

Diabetes Mellitus. Diabetes April 2009 vol. 58 no. 4 773-795

6. David Russel-Jones and Stephen Gough. Recent advances in incretin-based therapies. Clinical Endocrinology (2012)

77, 489-499

7. www.kimsonline.co.kr

: ()

7 2013 11

(, : HH833)

1. : () 1.00g, () 1.00g, () 0.66g, () 0.66g, () 0.66g, () 0.66g,

() 0.55g, () 0.55g, () 0.33g, () 0.33g, () 0.33g, () 0.16g

* : 1.16g

2. : 2.5g/

3.

() (), () () ,

, .

. () () ()

() . () , ,

. () () , , ()

() .

4.

5. : (), ()

6. : ,

7. : 1 7.5g 2~3

8.

9.

: , ( ), ,

: , , , ,

: , ,

*

10. : 36, , (1~30)

11. / : TSUMURA &CO./ ()

12. : HX010

Reference

1. DC()

2. , , 2005

3. , , 2002

: ()

,

, , , , ,

, , , ,

8 2013 11

( : 2013.10.31 / 2013.11.26) 1.

Labopar inj. 50mg/5mL (Ritodrine) 50MG ()

2. : , ,

3.

EMA, / ,

:

: 22 ~ 37 48

4.

: (2013.11.26)

:

- 22 37 (2013.12.16 )

( : 2013 12 5) .

/ e- , FAQ,

.

,

.

, .

: http://pharm.khnmc.or.kr

[]Muteran cap. 200mg

(Acetylcysteine)

,

: MCU 200

[]Winrho SDF inj. 1,500IU/3mL

(AntiD(Rho) Immunoglobulin)

[]Almarl tab. 10mg (Arotinolol)

, 40%

: CJ / A1

: , , google

: : , , , , , , ,

134-090 892

- -

TEL. 02-440-6977 / 02-440-6992 () FAX. 02-440-6984

http://pharm.khnmc.or.kr E-mail: rosa78@khnmc.or.kr