2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy...

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Lobeglitazone, A Novel PPAR-γ agonist with balanced efficacy and safety Kim, Sin Gon. MD, PhD. Professor, Division of Endocrinology and Metabolism Department of Internal Medicine, Korea University College of Medicine. 2013 International Conference on Diabetes and Metabolism

Transcript of 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy...

Page 1: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

Lobeglitazone,

A Novel PPAR-γ agonist with balanced efficacy and safety

Kim, Sin Gon. MD, PhD.Professor,Division of Endocrinology and MetabolismDepartment of Internal Medicine, Korea University College of Medicine.

2013 International Conference on Diabetes and Metabolism

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This symposium is sponsored by Chong Kun Dang Pharmaceutical Corp.I have received lecture and consultation fees from Chong Kun Dang.

Disclosure of Financial Relationships

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Pros• Good glucose lowering• Durability (ADOPT)• Insulin sensitizing

effects (especially in MS, NAFLD, PCOS etc)

• Prevention of new-onset diabetes (DREAM, ACT-NOW)

• Less hypoglycemia• Few GI troubles• Outcome data

(PROactive)

Cons• Adverse effects

(edema, weight gain,CHF, fracture or rare macular edema etc)

• Possible safety issues(risk of MI? – Rosi orbladder cancer? - Pio)

Pros & Cons of PPAR-γ agonist

So, there is a need to develop PPAR-γ agonist with balanced efficacy and safety

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1994 1997 1999 2000 2002 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Rosi, lipid profiles Rosi, lipid profiles

Dr. NissenDr. Nissen

Rosi (5)Rosi (5)

Pio (7)Pio (7)

PIO, bladder cancerPIO, bladder cancer

FDA, Black box

warning

FDA, Black box

warning

ADOPTADOPT BARI-2DBARI-2D

Rosi , CV safety

= no evidence

Rosi , CV safety

= no evidence

Tro out d/t

hepatotoxicity

Tro out d/t

hepatotoxicity

Rosi,

- REMS in USA

- Europe out

Rosi,

- REMS in USA

- Europe out

META analysis

(5,8)

META analysis

(5,8)RECORDRECORD

Dr. NissenDr. NissenDREAMDREAM

Rosi, Peak sale ($3.3 billion)

FDA, All diabetes

drug CV safety

FDA, All diabetes

drug CV safety

Discovery& Preclinical study Discovery& Preclinical study

2000.6-2004.6

Phase IPhase I Phase IIPhase II Phase IIIPhase III

CKD 5012004.11-2007.1 2007.3-2008.10 2009.11-2011.04

Lobeglitazone

Insulin Sensitizers : Several Issues

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Discovery & Preclinical study Discovery & Preclinical study

2000.06 - 2004.06

Phase IPhase I

Phase IIPhase II

Phase IIIPhase III

2004.11 - 2007.01

2007.03 - 2008.10

2009.11 - 2011.04

EfficacyEfficacy

ADMEADME SafetySafety

• PPAR activity• In vitro & vivo efficacy• Potent efficacy

• In vitro screening•Metabolites• CYP 450• DDI

• Repeated dose toxicity• Geno toxicity• Reproductive toxicity• Carcinogenic toxicity

CV Safety / (Bladder) Cancer / Liver Toxicity / Bone loss

Developmental Strategy

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Lobeglitazone (Duvie)

• PPAR-γ agonism4. MOA4. MOA

1. Structure1. Structure

N

N

OH3CO

NO

S

HNO O

H2SO4

3. Features3. Features • Insulin sensitizer• Favorable lipid profiles & Improves Metabolic Syndrome• Better safety (No bladder cancer in animal study)

2. Nomenclature2. Nomenclature • Durable (for a long time ) + Vie (a life), in French• A better life or longer life

C24H24N4O5S H2SO4 : MW = 578.62

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DNA microarray analysis

72373 68

158

26

Glucose and lipid metabolismGlucose and lipid metabolism

Rosi Pio

Lobe

311 28

Gene Expression

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In vitro study – PPARγ agonism

PPARγ

1000

nM

1000

nM

1000

nM

3.0

2.5

2.0

1.0

1.5

0.5

0

DM

SO

1 nM

10 n

M

100

nM

DM

SO

1 nM

10 n

M

100

nM

DM

SO

1 nM

10 n

M

100

nM

PioglitazoneLobeglitazone

Rosiglitazone

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Dose(mg/kg/

d)

B.W (g)

Glucose(mg/dl)

Insulin(ng/ml)

TG(mg/dl)

NEFA(μEq/L)

Control - 359.8 ± 4.8 402.1 ± 15.4 16.6 ± 1.4 625.0 ± 46.0 685.7 ± 80.9

Lobeglitazone

0.03 491.4 ± 10.2*** 115.4 ± 8.1*** 27.0 ± 5.7 526.8 ± 50.5 206.1 ± 44.1***

0.1 530.9 ± 10.7*** 108.1 ± 5.4*** 10.2 ± 0.3* 282.0 ± 18.3*** 50.1 ± 4.0***

0.3 513.1 ± 11.2*** 105.6 ± 4.4*** 8.6 ± 1.1** 145.2 ± 9.8*** 15.7 ± 3.1***

Pioglitazone

10 522.0 ± 8.6*** 99.5 ± 1.7*** 10.0 ± 1.0* 213.8 ± 22.0*** 62.9 ± 12.6***

30 512.4 ± 11.7*** 103.4 ± 2.6*** 7.0 ± 0.6*** 159.3 ± 10.5*** 23.9 ± 3.3***

p.o., 28 days / Mean± SD. *<0.05, **<0.01, ***<0.001TG : triglyceride. NEFA : non-esterified fatty acid.

In vivo study – ZDF rats

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1 Insulin Sensitizers and CV safety

2 Insulin Sensitizers and (Bladder) cancer

3 Insulin Sensitizers and Liver toxicity

4 Insulin Sensitizers and Bone loss

Safety – Toxicology data

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Effect of Lobeglitazone on Plasma volume

Group Dose(mg/kg)

B.W.(g)

Heart Wt. Plasma Volume

g/kg Inc.% ml/kg Inc.%

Vehicle - 299 ± 26 2.91 ± 0.07 - 50.0 ± 3.5 -

Lobeglitazone

1 294 ± 13 2.91 ± 0.11 - 54.4 ± 5.0 8.8

3 292 ± 16 2.93 ± 0.14 0.7 58.0 ± 8.7 16.0

10 308 ± 26 2.95 ± 0.11 1.4 63.3 ± 3.8* 26.6

Pioglitazone10 301 ± 11 2.86 ± 0.20 -1.7 56.5 ± 3.0* 13.0

30 311 ± 26 2.90 ± 0.17 -0.3 57.5 ± 3.4* 15.0

p.o., qdx5/week, 4 weeksSD rat

Insulin Sensitizers & CV safety

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1

2

Carcinogenic studies

Bladder tumor studies

Rodents [Mice & Rats]

Rodents [Rats]

Insulin Sensitizers & (Bladder) Cancer

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Carcinogenicity in Mice

CompoundsDose

(mg/kg)LOAEL

(mg/kg)Neoplastic lesions AUC

(㎍.h/ml)Exposure

ratio

Lobeglitazone 0.2, 1.0, 6.0 > 6.0 - > 18 > 26

Rosiglitazone 0.4, 1.5, 6.0 > 6.0 - > 26 > 8.7

Pioglitazone 3, 10, 30, 100 30Pheochromocytoma

Leiomyosarcoma180 14

Troglitazone 50, 400, 800 400Hemagiosarcoma

Hepatocelluar carcinoma- 2

Muraglitazar 1, 5, 20 20 Adenoma 304 62

Insulin Sensitizers & (Bladder) Cancer – (1)

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Uninary bladder tumors with pioglitazone [Male rats]

Urinary Bladder LesionIncidence by dose (mg/kg/day)

Vehicle Placebo 1 4 8 16 63

Males

Carcinoma, transitional cell 0 0 0 2 3 5 4

Transitional tumor, benign 0 0 0 0 4 2 2

Transitional hyperplasia 4 3 1 4 12 12 8

…… increased incidence of urinary bladder tumor ≥ 4 mg/kg/day (40 mg/human).

From pioglitazone NDA files

Insulin Sensitizers & (Bladder) Cancer – (2)

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Uninary bladder hyperplasia with Lobeglitazone

Sex Male Female

Dose (mg/kg/day) Vehicle 0.03 0.12 1.0/0.24 Vehicle 0.03 0.06 0.12

Carcinoma,Transitional cell

- - - - - - - -

Transitional tumor, benign

- - - - - - - -

Urinary Bladder

Transitional cell hyperplasia

0 1 3 1 0 1 2 7

A 2-year carcionogenicity study in Rats

Insulin Sensitizers & (Bladder) Cancer – (3)

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Scheme of 1o metabolic pathways involved in TGZ metabolism

Liver toxic metabolite

Drug metabolism and disposition. 2004;32:639-646.

Insulin Sensitizers & Liver toxicity – (1)

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Lobeglitazone Rosiglitazone Troglitazone

Clinical dose (mg) 0.5 8 600

Liver : plasma ratio (rat) 0.85 0.5 15

Biliary recirculation No No Yes

Quinone metabolites No No Yes

In vitro liver toxicity (IC50) 57.6 uM 190 uM 37.5 uM

Half-life in humans (h) 9.5 (M), 15 ( F) 4 16-34

Cmax (liver) 0.085 μM 0.85 μM 95 μM

In vitro liver toxicity : Cmax 676 223 0.39

Insulin Sensitizers & Liver toxicity – (2)

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Insulin Sensitizers & Bone Loss

Oil red O staining

MSC, male wistar rat (6 wks)

Rosiglitazone

Pioglitazone

Lobeglitazone

0.0

0.2

0.4

0.6

0.8

1.0

1.2

con 5nM 50nM 500nM 5uM 50uM

Rosiglitazone

Pioglitazone

Lobeglitazone

ALP activity

Relative Increase

Page 19: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

A 52-week oral capsule toxicity study in monkeys

- No increased toxicity compared to pioglitazone

Lobeglitazone

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An Evaluation of Glycemic Effects of LobeglitazoneMonotherapy in Patients With Type 2 Diabetes Mellitus

Monotherapy

Phase III clinical trial

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Study Design - Monotherapy

� Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM

� Patients: 173 patient (Type 2 DM for a duration of at least 3 months)

� Dose: Lobeglitazone 0.5mg vs matching placebo (a 2:1 ratio)

� Treatment period: 24 weeks (extension to 52 weeks)

� Primary endpoint: HbA1c change from baseline

� Study sites: 5 sites in Korea

Visit 2 Visit 4 Visit 5 Visit 7

Randomization

Week-10 ~ -6

Week-2

Day0

Week4

Week10

Week24

Visit 3Visit 1

Run-in period(2 weeks)

Treatment period (24 Weeks)

Screening period(4 Weeks)

Visit 6

Week16

Placebo

Lobeglitazone 0.5 mgPlacebo(single blind)

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Efficacy - HbA1c (Monotherapy)

Difference at 24 weeks

-0.2

0.0

0.2

0.1

-0.4

-0.6

-0.7

-0.1

-0.3

-0.5

0.09

-0.57

Mea

n ch

ange

from

bas

elin

e (%

)

0.66 % DifferenceP < 0.0001

Study week

7.8

8

8.2

7.6

7.2

7

7.4

HbA1c

(%

)

0 4 10 16 24

7.958.05 8.03

7.968.04

7.757.71 7.49

7.267.18

*

Placebo (N=43) Lobeglitazone 0.5 mg (N=87)

: P < 0.05 vs Baseline*

Lobeglitazone 0.5 mg (N=87)Placebo (N=43)

� A significant reduction in HbA1c was observed with lobeglitazone versus placebo

Page 23: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

� The HbA1c target of <7% was achieved significantly more often in the lobeglitazonegroup compared to the placebo group

Efficacy – Response rate (Monotherapy)

A1c target achievement rate (%) <7.0 %

40

60

50

10

0

30

20

11.63%

51.72%

P < 0.0001

Lobeglitazone 0.5 mg (N=87)Placebo (N=43)

Page 24: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

Effects on various gluco-metabolic andlipid parameters of lobeglitazone

Lobeglitazone (n=110) Placebo (n=58)

HOMA-IR 3.51 ± 1.86 2.80 ± 1.58c 4.30 ± 3.82 4.70 ± 5.25 0.002

HOMA- β 44.42 ± 23.02 54.93 ± 34.16c 44.48 ± 26.65 45.05 ± 35.89 0.0277

Total cholesterol

(mg/dL)178.70 ± 32.08 184.70 ± 34.48a 188.26 ± 37.66 193.10 ± 42.63 0.7191

Triglyceride (mg/dL) 137.51 ± 74.72 118.45 ± 56.24b 177.14 ± 119.34 193.28 ± 160.61 0.0006

HDL cholesterol

(mg/dL)48.69 ± 12.78 52.99 ± 13.62c 46.33 ± 13.56 47.09 ± 11.57 0.0038

LDL cholesterol

(mg/dL)109.00 ± 32.25 109.95 ± 32.89 114.76 ± 34.01 112.12 ± 29.83 0.6358

Small dense LDL (%) 8.10 ± 6.70 6.40 ± 6.55a 9.51 ± 6.81 10.13 ± 7.49 0.0033

Free Fatty acid (uEq/L) 622.28 ± 214.18 561.89 ±236.24a 699.57 ± 262.28 698.57 ± 253.69 0.0047

Apolipoprotein B

(mg/dL)80.15 ± 19.64 76.01 ± 18.73b 85.93 ± 21.85 86.43 ± 20.19 0.0046

Page 25: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

� Lobeglitazone 0.5 mg significantly lowered the proportion of subjects with metabolic syndrome

Metabolic syndrome (Monotherapy)

-10

-6

0

-4

-16

-8

-12

0

-14 %

Abso

lute

diff

eren

ce in

pro

port

ion

of M

S (%

)

50

60

30

10

0

40

20

60.34

pro

port

ion

of s

ubje

cts

with

met

abolic

syn

dro

me

(%)

P = 0.0223

14%▼P = 0.0039

70

60.3455.45

41.82

-14

-2

0 week 24 week 0 week 24 week

Lobeglitazone 0.5 mgPlacebo

Lobeglitazone 0.5 mgPioglitazone 15 mg

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Hypoglycemia & Weight (Monotherapy)

� Hypoglycemia was not observed in both treated groups

� More weight gain was observed in the lobeglitazone group than in the placebo group, about 1kg over 24 weeks

: P < 0.05 vs Baseline*

Placebo (N=58)

50

70

30

10

0

40

20

65.93

Wei

ght

(kg

)

80

66.55 67.38

0 week 24 week 0 week 24 week

*

60

*65.37

P < 0.0001

Hypoglycemia

PlaceboN (%)

0 (0%)

LobeglitazoneN (%)

0 (0%)

< Incidence rate of hypoglycemia >

Lobeglitazone 0.5 mg (N=112)

Page 27: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

Adverse events summaryPlacebo N (%)

Lobeglitazone 0.5 mgN (%)

P value

Number of patients 58 112 -

Number of patients experienced an AE 30 (51.72) 55 (49.11) 0.7463

Number of patients experienced a SAE - 4 (3.57) 0.3005

Summary of AE (Monotherapy)

Number of patients experienced an ADR 3 (5.17) 10 (8.93) 0.5461

• Serious AEs in the lobeglitazone 0.5 mg group included lung cancer, traumatic cerebral

hemorrhage, cerebrovascular accident (underlying atrial fibrillation), and right scrotal

laceration and hemorrhoidectomy. These serious AEs were not considered by the

investigators to be related to the study medication.

• In addition, heart failure, ischemic heart disease, renal insufficiency, or bone

fracture was not observed in either group.

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� Effectively controlled blood glucose(Significantly reduced HbA1c)

� Increased target HbA1C achievement rates

� Improved insulin resistance and beta-cell function

� Improved lipid profile(Significantly reduced triglyceride, small dense LDL-C and increased HDL-C)

� Lowered the proportion of subjects with metabolic syndrome

Summary (Monotherapy)

� Lobeglitazone 0.5 mg

� The safety profile was comparable between the two groups and lobeglitazone was well tolerated

Page 29: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

Efficacy and Safety of Lobeglitazone Versus Pioglitazone

When Added to Metformin

Combination therapy

Phase III clinical trial

Page 30: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

� Objective: To assess the efficacy and safety of Lobeglitazone 0.5 mg compared with Pioglitazone 15 mg as an add-on therapy in patients with T2DM

� Patients : 253 patient (Inadequate glycemic control while taking metformin alone (HbA1c 7~10%))

� Dose: Lobeglitazone 0.5mg vs Pioglitazone 15 mg

� Treatment period: 24 weeks (extension to 52 weeks)

� Primary endpoint: HbA1c change from baseline

� Study sites: 18 sites in Korea

Study design - Combination therapy

Visit 2 Visit 4 Visit 5 Visit 6Week

-15 ~ -7Week

-3Day1

Week4

Week12

Week24

Visit 3Visit 1

Run-in period(2주)

Treatment period(24주)

Screening

Metformin Placebo+ Metformin

Lobeglitazone 0.5 mg QD + Pioglitazone 15 mg placebo

Pioglitazone 15 mg QD + Lobeglitazone 0.5 mg placebo

Stabilization period(8주)

Randomization

Page 31: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

Efficacy - HbA1c (Combination therapy)

� Lobeglitazone 0.5mg showed non-inferiority in HbA1c reduction compared to pioglitazone 15mg

7.80

8.00

7.60

7.20

7.00

7.40HbA1c

(%

)

0 4 12 24 week

7.93

7.79

7.40

7.17

7.92

7.74

7.31

7.100 week 24 week

7.60

7.80

7.20

6.80

6.60

7.40

7.00

7.93

8.00

7.92

7.17 7.10

0.82 %Difference

0.76 %Difference

**

: P < 0.05 vs Baseline*

Pioglitazone 15mg (N=103) Lobeglitazone 0.5mg (N=97)Lobeglitazone 0.5 mg (N=97)Pioglitazone 15mg (N=103)

Difference at 24 weeksStudy week

Mea

n ch

ange

from

bas

elin

e (%

)

Page 32: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

� Proportion of patients achieving HbA1c < 7 % in the lobeglitazone group was comparable to the pioglitazone group

Response rate (Combination therapy)

Proportion of patients achieving HbA1c < 7 %

48.0

52.0

50.0

44.0

36.0

42.0

38.0

49.5151.55

NS

46.0

40.0

Pioglitazone 15 mg (N=103) Lobeglitazone 0.5 mg (N=97)

Page 33: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

Insulin resistance and ß cell function(Combination therapy)� Both pioglitazone 15mg and lobeglitazone 0.5mg significantly improved insulin

resistance and β cell function

-0.40

0

-0.20

-1.20

-1.60

-0.60

-1.00

-1.34-1.49

Mea

n ch

ange

from

bas

elin

e

-0.80

6.00

9.00

7.00

2.00

0

5.00

3.00

7.70M

ean

chan

ge

from

bas

elin

e

4.00

0.015

0.003

0

0.012

0.006

0.013 0.013

Mea

n ch

ange

from

bas

elin

e

0.009

HOMA-β QUICKI

**

*HOMA-IR

NS

36.43%▼3.93%▲

-1.40 1.00

8.00

34.18%▼

6.82

16.67%▲15.21%▲

NS

*

*

NS

*

3.97%▲

: P < 0.05 vs Baseline*

Lobeglitazone 0.5 mg (N=97)Pioglitazone 15 mg (N=103)

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Lipid profile - TG, FFA (Combination therapy)

� Both pioglitazone 15mg and lobeglitazone 0.5mg significantly improved triglyceride and free fatty acid levels

-40

-20

0

-10

-70

-90

-30

-50-59.70

Mea

n ch

ange

from

bas

elin

e (m

g/d

L)

-20.0

-10.0

0

-5.0

-30.0

-40.0

-45.0

-15.0

-25.0

-35.0

-17.48-14.7

Mea

n ch

ange

from

bas

elin

e (m

g/d

L)

*

NS

free fatty acid

11.09%▼10.38%▼

9.20%▼

12.45%▼

NS

Triglyceride

-60

-80

*

: P < 0.05 vs Baseline*

-84.60

*

Lobeglitazone 0.5 mg (N=97)Pioglitazone 15 mg (N=103)

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Lipid profile-HDL-C, small dense LDL-C (Combination therapy)� Both Pioglitazone 15mg and Lobeglitazone 0.5mg significantly improved HDL-C

and small dense LDL-C levels.

-0.8

-0.4

0

-0.2

-1.2

-1.4

-0.6

-1.0

-1.25M

ean

chan

ge

from

bas

elin

e (m

g/d

L)

*

5

7

3

1

0

4

2

Mea

n ch

ange

from

bas

elin

e (m

g/d

L)

HDL-C

13.15%▲29.48%▼

*

10.07%▲

small dense LDL-C

16.38%▼

6 6.38

4.98

*NS

-0.78

NS

: P < 0.05 vs Baseline*

Lobeglitazone 0.5 mg (N=97)Pioglitazone 15 mg (N=103)

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Subgroup Analysis – BMI (Combination Therapy)

-0.40

-0.20

-0.30

-0.70

-0.80

-0.50

-0.60

-0.85HbA1c

(%

) ch

ange

from

bas

elin

e -0.10

0

-0.93

-0.61-0.54

*

*

: P < 0.05 vs Baseline*

-0.90

-1.00

*

*< BMI 25 kg/m2 ≥ BMI 25 kg/m2

Lobeglitazone 0.5 mg (N=97)Pioglitazone 15 mg (N=103)

NS NS

Page 37: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

-0.40

-0.20

-0.80

-0.60

-0.88

HbA1c

(%

) ch

ange

from

bas

elin

e

0

NS

-1.02

-0.60-0.53

*

*

: P < 0.05 vs Baseline*

-1.00

-1.20

NS

*

*

Male > 90 or Female > 80Male < 90 or Female < 80

Lobeglitazone 0.5 mg (N=97)Pioglitazone 15 mg (N=103)

Subgroup Analysis – Waist Circumference (Combination Therapy)

Page 38: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

Hypoglycemia & Weight (Combination therapy)

� The incidence of hypoglycemia and weight gain were not different between the two groups

50

70

30

10

0

40

20

66.11

1.3%▲

Wei

ght

(kg

)

80

67.14 67.28 68.31

0 week 24 week 0 week 24 week

2.50

3.00

1.50

0.50

0

2.00

1.00

2.40

Hyp

ogly

cem

ia e

vent

(%)

NS

*

0.78

60

1.1%▲

NS

*

: P < 0.05 vs Baseline*

Lobeglitazone 0.5 mg (N=97)Pioglitazone 15 mg (N=103)

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Adverse events summaryLobeglitazone 0.5 mg

N (%)Pioglitazone 15 mg

N (%)P value

Number of patients 128 125 -

Number of patients experiencing an AE 66 (51.56) 64 (51.20) 0.9540

Number of patients experiencing an SAE 7 (5.47) 6 (4.80) 0.8096

Summary of AE (Combination therapy)

Number of patients experiencing an ADR 8 (6.25) 6 (4.80) 0.6140

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Summary (Combination therapy)

� A1c reduction

� Achievement rate in HbA1c goal

� Improvement in insulin resistance, β cell function, and lipid profiles

� Lobeglitazone 0.5mg was not inferior to pioglitazone 15mg regarding,

� The safety profile was comparable between the two groups and lobeglitazone was well tolerated

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Conclusion

� Lobeglitazone 0.5 mg showed improvements in glucose and lipids endpoints with a favorable safety profile. The results support lobeglitazone as a promising option for treating type 2 diabetes, especially in patients with metabolic syndrome

Page 42: 2013 International Conference on Diabetes and …2013-11-15 · Study Design -Monotherapy Objective: To assess the efficacy and safety of Lobeglitazone 0.5mg in T2DM Patients: 173

Thank you for

Your Attention !