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Improvement of Insulin

Resistance with Inlacin


(Bioactive Fraction DLBS 3233)

Oleh :
Billy
PT Dexa Medica

PHYTOCHEMICALS
No

Medicinal Plants

Contain of

Usage

Catharanthus roseus(formerly
known asVinca rosea)

Vincristine
Vinblastine

Cancer therapy

Digitalis purpurea

Digitoxin

Heart disease

Taxus baccata

Paclitaxel

Cancer therapy

Papaver somniferum

Opium

Analgetic

Galega officinalis

metformin

OAD

THE HOME OF OUR RESEARCH


ACTIVITIES

exa Laboratories of Biomolecular Science (DLBS) was conceived


and started with occupying the present facility and being active
drug discovery and nutraceuticals research

Drug Discovery: from Basics


to Clinic

DEVELOPMENT
PROCESS
Fractionatio
n, Isolation,
Synthesis

Inlacin

Extraction &
Fractionation

Fractionation
followed by
Molecular
Screening

Extraction
Drying

DLBS, 2010

FACILITIES

Tandem Chemistry Expression Bioassay


System (TCEBS)

is a systematic screening methodology dedicated to find the most active and


potent candidates for DLBS products. It is usually followed by bioassay
system that utilizes gene expression and protein array techniques

October 2010

August 2011

January 2011

June 2011

Bioactive Fraction
DLBS3233
Target gen/Target Protein

DLBS3233
(Lagerstroemin dan
Cinamommum sebagai
bioactive)

Lagerstroemin, an
ellagitannin

Improvement of Insulin
Resistance with INLACIN
(DLBS3233)

Inlacin (DLBS3233)
MECHANISM
Phosporylation on the right
insulin receptor

Up regulator PPAR and PPAR

GLUT-4 translocation from


citoplasma to membran

TNF

DLBS3233 promotes Tyrosine


phosphorylation of the Insulin Receptor
Protein Increasing PI3 Kinase and Akt

1,7x lebih besar dari


kontrol

1,5x lebih besar dari


kontrol

DLBS 3233 INCREASES PPAR GAMMA &


PPAR DELTA EXPRESSION

1,8x lebih besar dari


kontrol

DLBS3233 INCREASES TOTAL GLUT-4


IN ADIPOCYTES

DLBS 3233 meningkatkan


sintesis & translokasi GLUT4

DLBS 3233 INCREASES ADIPONECTIN


EXPRESSION, WHILE DECREASES
RESISTIN EXPRESSION

CLINICAL
STUDY

INLACIN CLINICAL STUDY


No

Trial ID

Projects

Therapy

1.

DLBS32
330209

Safety study in
Healthy volunteers
(Phase-1)
Prof. K Suastika, Dr. RR
Tjandrawinata

2.

DLBS32
330309

Preliminary study in
T2DM
RS Sanglah, Denpasar
Prof. Ketut Suastika

3.

DLBS32
330411

T2DM : Inlacin + any DLBS3233 capsule 100


other OAD
mg (od) + current OAD
RS Soetomo, Surabaya treatment (stable dose)
Prof. Askandar
Tjokroprawiro

Sampl
e
size
6

Inlacin vs Placebo

20

54

No

Trial ID

Projects

Therapy

Sampl
e size

4.

DLBS32 Pre DM
33-0711 RS M.Djamil, Padang
Prof. Asman Manaf

DLBS3233 capsule
50 mg (od), titration
at W4 to 100 mg (if
necessary) vs
placebo capsule of
DLBS3233 (od),
titration at W4 (if
necessary

80

5.

DLBS32 PCOS
33-0811 RS Cipto
Mangunkusumo,
Dr. Andon +
RSHS, Bandung,
Dr. Wiryawan

DLBS3233 capsule
100 mg (once daily)
and placebo tablet of
Metformin (twice
daily) vs Metformin
tablet 500 mg
(twice daily) and
placebo capsule of
DLBS3233 (once daily)

124

6.

DLBS32 T2DM (newly


33-0912 diagnosed): Inlacin

DLBS3233 capsule
100 mg (od) vs

104

SAFETY STUDY IN HEALTHY VOLUNTEERS


(PHASE-1)
DLBS 3233

PRELIMINARY STUDY IN T2DM


(INLACIN vs PLACEBO)
Fasting Plasma
Glucose
Post-prandial
Plasma Glucose
HbA1c level
HOMA-IR
Lipid Profile

FASTING PLASMA
GLUCOSE

POST-PRANDIAL PLASMA
GLUCOSE

HbA1c REDUCTION 6
WEEKS

Diabetes
Complication

Complication Risk Reduction

Diabetes-related
death

21%

Myocardial Infarction

14%

Stroke

12%

Peripheral vascular
disease

43%

HOMA-IR REDUCTION

LIPID PROFILE

PROFILE SAFETY
Paramete
r
SGPT

Group

Placebo
DLBS 50
mg
Alkalin
Placebo
Phosphata DLBS 50
se
mg
Serum
Placebo
Creatinin DLBS 50
mg

Baseline
Mean (SD)

End of
study
Mean (SD)
18.20 (12.38) 18.33 (13.63)
30.50 (10.81) 21.86 (16.28)
77.30 (6.05)
75.63 (21.59)

77.22 (6.40)
73.43 (9.67)

0.76 (0.14)
0.78 (0.15)

0.76 (0.19)
0.79 (0.16)

Phase-III Clinical Study

DLBS3233
IN PRIMARY PREVENTION OF TYPE
2 DIABETES MELLITUS
[DIPPER-DM]
Study site : M.Djamil Hospital, Padang
Principal Investigator : Prof. Dr. dr. Asman Manaf, SpPD-KEMD

2-HOUR POST PRANDIAL GLUCOSE


LEVEL AFTER 8 AND 12 WEEKS OF
TREATMENT
170

165

164.97
160.37

160

155

151.06
150

145.94
Glucose Level (mg/dL)

DLBS 3233

145

Placebo
140

135

130

125

120

Baseline

143.36
Week 8

137.95
Week 12

REDUCTION IN FASTING TG
Reduction in Fasting Tryglyceride
0

Week 8

Week 12

p = versus baseline
level in each group

-5

-10

*P =
0.082

*P =
0.080

-12.71
Triglyceride Level (mg/dL)

-15

-15.06

-20
*P =
0.007

*P =
0.003

-25

-26.2
-30

-28.5

DLBS 3233
Placebo

SURABAYA INLACIN
STUDY
Study in patient with diabetes

INSULIN
RECEPTOR BINDING AFFINITY
1
DECREASED TNF
5

(due to PPAR
FFA, then PKC & , & Apn)
thus SERINE
PHOSPHORYLATION (I.R.)

RESISTIN

2
TYROSINE PHOSPHORYLATIO
TYROSINE
PHOSPHORYLATION
INSULIN
RESISTANCE (I.R.):

DLBS-3233
(INLACIN)
THE NOVEL
INSULIN SENSITIZER
2016

4 STIMULATE GLUT-4

FROM
CYTOPLASM TO CELL
TRANSLOCATION
MEMBRANE
8
ACC1 & ACC2,
Malonyl CoA
-Oxidation, FFA

ADIPONECTIN

PPAR & PPAR UP


REGULATOR
GLUT-4 SYNTHESIS
&:
NUMBER, HDL

DLBS-3233 : LAGERSTROEMIA SPECIOSA & CINNAMOMUM BURMANII


BIOACTIVE FRACTION DLBS3233 : LAGERSTROEMIN, AN ELLAGITANNIN

in (DLBS3233) : the Novel Insulin Sensitizer with 8 Unique Mechan

Dec 2010, Tjandrawinata et al 2010, 2013, Nailufar et al 2011, Tandrasasmit


(Illustrated : Tjokroprawiro
2011-2013)

Delta Fasting Plasma Glucose


(mg/dL)

THE RESULTS OF SURABAYA-INLACIN STUDY


REDUCTION(SIS)
IN FASTING
PLASMA
2012-2013
1
GLUCOSE (FPG)

0.0
0-

5.0
010.0
015.0
020.0
025.0
030.0
035.0
0

18.98

FPG

11.71

Week 6
Week
12

p = 0.298
p = 0.072

Week

Delta vs
baseline

SD

p versus
baseline

FASTING PLASMA GLUCOSE

Mean

SD

Fasting plasma glucose at baseline (mg/dL)


Fasting plasma glucose at Week 6 (mg/dL)

187,10
167,00

72,25
58,85

-18,98

69,14

0,072

Fasting plasma glucose at Week 12 (mg/dL)

175,64

65,42

-11,71

64,21

0,298

THE RESULTS OF SURABAYA-INLACIN STUDY


(SIS) 2012-2013
SIGNIFICANT
IN
SIGNIFICANT REDUCTION
REDUCTION
IN 1-h
1-h POST
POST PRANDIAL
PRANDIAL
Delta 1-h Post Prandial Plasma
Glucose (mg/dL)

0.0
05.00
10.0
0
15.00
20.0
0
25.0
0
30.0
0
35.0
0
40.0
0

GLUCOSE
GLUCOSE (PPG)
(PPG)

PPG

23.31

26.06
Week 6
Week
12

*p=
0.047

Week

1-hr POST PRANDIAL GLUCOSE

*p=
0.021
Delta vs
baseline

SD

p versus
baseline

Mean

SD

One hour plasma glucose at baseline


(mg/dL)
(mg/dL)
One hour plasma glucose at Week
6

275,46
250,22

80,88
70,84

-23,31

76,14

0,047*

(mg/dL)
One hour plasma glucose at Week
12

249,92

74,13

-26,06

70,08

0,021*

THE RESULTS OF SURABAYA-INLACIN STUDY


SIGNIFICANT
SIGNIFICANT REDUCTION
REDUCTION
(SIS)IN2012-2013
2

Delta A1C (%)

1C
0.0A1C
00.1
00.200.300.400.500.600.700.800.901.00

A1C

-0.36

A1C

12% subjects
reached A1c <
7.0% within 12
weeks of
treatment
Week 6
Week
12

-0.65

*p=
0.009

Week

*p=
0.001
Delta vs
baseline

SD

p versus
baseline

Mean

SD

A1c at baseline (%)

9,67

2,11

A1c at Week 6 (%)

9,34

2,21

-0,36

1,13

0,009*

A1c at Week 12 (%)

9,02

2,04

-0,65

1,58

0,001*

THE RESULTS OF SURABAYA-INLACIN STUDY


(SIS)
2012-2013
3 SIGNIFICANT REDUCTION
IN HOMA-R
SIGNIFICANT REDUCTION IN HOMA-R

Delta HOMA-IR

0.0
00.2
0
-0.40

-0.50
-0.77

-0.60

HOMA
-R

-0.80
-1.00
-1.20
-1.40

HOMA-R

Week 6
Week
12

p = 0.281
*p=
0.043

Week
Delta vs
baseline

SD

p versus
baseline

Mean

SD

HOMA-R calculation at baseline

4,59

3,45

HOMA-R calculation at Week 6

3,69

2,41

-0,77

3,19

0,043*

HOMA-R calculation at Week 12

4,09

2,72

-0,50

3,45

0,281

RESULTS, SUMMARY AND CONCLUSIONS OF


THE SURABAYA-INLACIN
PLASMA
GLUCOSE
STUDY
(SIS)
2012-2013
1 FASTING

18.98 mg/dL (W 6: 10.14%) p = 0.072


11.71 mg/dL (W 12: 6.26%) p = 0.298 (NS)
+0.42 kg (W 6) p = 0.218
+0.42 kg (W 12) p =
2 1h PRANDIAL PLASMA
0.412
GLUCOSE
23.31 mg/dL (W 6: 8.46%)
p = 0.04

9 BODY WEIGHT

8 ADIPONECTIN

(Apn)
+0.45g/mL
(W 6: 8.99%)
p = 0.148 (NS)
+1.05g/mL (W 12: 21.18%)
p = 0.001

7TRIGLYCERIDE
-8.39 mg/dL (p = 0.405)
-8,00 mg/dL (p =
0217)

TOTAL

-11.49 mg/dL (W 6:
CHOLESTEROL
5.05%)
p=
-10.39 mg/dL
0.002(W 12:
4.56%)
p=
0.013

26.06 mg/dL (W 12: 9.46%) p = 0.0

RESULTS OF THE STUDY


ADD-ON Tx WITH 100 mg
INLACIN
n = 50, STUDY PERIOD 12
WEEKS
SURABAYA DIABETES AND
NUTRITION CENTER
2013

5-10.04 mg/dL (W LDL


6:

CHOLESTEROL
6.93%)
p=
-10.59 mg/dL
0.006 (W 12:
7.31%)
p=
0.020

A1C

-0.36 % (W 6: 3.69%) p
= 0.009
-0.65 % (W 12:
6.76%)
p=
0.001

HOMA-R

-0.77 (W 6: 16.84%) p =
0.043
-0.50 (W 12: 10.88%) p =
0.281 (NS)

W-12, HOMA-R Pts (n=25 no routine excercise NS) (n=25 routine

DOSAGE AND PACK OF


INLACIN
PRODUCT

PACK

HNA/BOX

HNA/CAPSULE

DOSAGE

INLACIN 50 mg

BOX, 5 STRIPS
@ 6 CAPSULES

Rp. 120.000,-

Rp. 4.000,-

Once daily

INLACIN 100
mg

BOX, 5 STRIPS
@ 6 CAPSULES

Rp. 150.000,-

Rp. 5.000,-

Once daily

DOSAGE:
Newly Diagnosed DM: 1 x 50-100 mg/ day
ADD ON with the other OADs: 1 x 100 mg/day

CONCLUSIONS
80% incidence of type 2 diabetes is caused by
insulin resistance
INLACIN is a bioactive fraction DLBS3233
INLACIN can improve insulin resistance
through four working mechanisms, namely:
1)
2)
3)
4)

Phosporylation on the right insulin receptor


Up regulator PPAR and PPAR
GLUT-4 translocation from citoplasma to membran
TNF

INLACIN
PUBLICATION

http://www.foodnavigator-asia.com/Business/Indonesianherbal-diabetic-drug-to-target-EU-and-Asia

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