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Management of Pre Diabetes

Slide Deck
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In Indonesia, Glucobay is licensed for:
Additional therapy in association with diet in patients with diabetes mellitus.
Impaired glucose tolerance (IGT)*, in combination with diet and exercise.

*Defined as 2 hour post-glucose load plasma concentration (2HPG) between 7.8 and 11.0 mmol/L (140-200mg/dL) and fasting
values between 6.1-6.9 and 7.0 mmol/L (100-125 mg/dL).

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Pre Diabetes is

When a person's blood glucose levels are higher than

normal but not high enough for a diagnosis of diabetes

ADA Diagnostic Criteria

Clinical Practice Recommendation 2010
No. Parameter Normal Pre Diabetes Diabetes

1. Fasting Plasma Glucose <100 100125 126

2. 2-h plasma glucose on <140 140199 200
OGTT (mg/dl)
3. HbA1C (%) <5.7 5.7 6.4 6.5

ADA Diagnosis Criteria

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Why its important to treat Pre Diabetes

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NHANES: National Health and Nutrition Examination Survey
NHANES: National Health and Nutrition Examination Survey
Janka HU. Fortschr Med 1992;110:637-41
Janka HU. Fortschr Med 1992;110:637-41

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DECODA: Pre Diabetes is associated with
an increased risk of mortality

DECODA (n=6,817)
Multivariate hazard ratio

3.0 All-cause mortality CVD mortality

p=0.001 p<0.001
2.0 p=0.006 p<0.001
<6.1 6.16.9 7.0 <7.8 7.811.0 11.1
FPG (mmol/L) 2hPG (mmol/L)

Nakagami T, et al. Diabetologia 2004;47:38594.

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Relationship between postprandial plasma
glucose levels and CVD mortality

Honolulu 19991 Pacific and
Heart Study Indian Ocean
19877 19992

Rancho Postprandial Funagata

Bernardo Study 19986 CVD Diabetes Study
plasma death 19993

Diabetes Whitehall, Paris and

Intervention Study Helsinki Study
19965 19984

1. DECODE. Lancet 1999;354:61721. 2. Shaw JE, et al. Diabetologia 1999;42:105054.

3. Tominaga M, et al. Diabetes Care 1999;22:92024. 4. Balkau B, et al. Diabetes Care 1998;21:36067.
5. Hanefeld M, et al. Diabetologia 1996;39:157783. 6 Barrett-Connor E, et al. Diabetes Care 1998;21:12369.
7. Donahue RP, et al. Diabetes 1987;36:68992.

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Postprandial hyperglycaemia is associated
with an increased risk of CVD
Singapore National Health Survey 1992 (n=3,568)


3.0 Individuals with IGT
had a higher risk of
Hazard ratio

ischaemic heart
2.0 disease than those
1.5 with NGT
in each FPG
1.0 category
<5.6 5.66.0 >6.0
FPG level (mmol/L)
Tai ES, et al. Diabetes Care 2004;27:172834.

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IDF Consensus Statement 2007

Earlier detection of people with IGT and others at high

risk, followed by interventions to delay or prevent type 2
diabetes and improve glucose control, can result in
clinically important reductions in the incidence of
diabetes and its complications and co-morbidities.

Alberti KGMM, et al. Diabet Med 2007;24:45163

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IDF recognises that PPHG increases the
risk of macrovascular complications
Is postmeal hyperglycaemia harmful?

IDF. Guideline for management of postmeal glucose, 2007


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Page 12 RTD Pre Diabetes Glucobay
How to help screen pre Diabetes patients?

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FINDRISC (Finnish Diabetes Risk Score):
Detection of people at high risk for diabetes
A self-administreted one-page
8 questions, with categorized answers
Waist circumference
Physical activity
Daily consumption of fruits, berries
or vegetable
History of antihypertensive drug
History of high blood glucose
Family history of diabetes

Recommended in
ESC and EASD Guidelines1
Adapted from: http://www.diabetes.fi/english/risktest/
Jaakko Tuomilehto et al. (2010) Diabetes Prevention in Practice ; 9-18

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Which glycemic standard should we use to
optimize diabetes management: PPHG, FBG or

Current glycemic recommendations

Benefits of glycemic control
Optimizing control
Link between FPG and CVD
PPHG as a better predictor of CV risk than FPG
Link between HbA1c and CVD
Role of PPHG in HbA1c
Treatment of PPHG overall effects

CVD, cardiovascular disease; FPG, fasting plasma glucose;

PPHG, postprandial hyperglycaemia; HbA1c, glycosylated haemoglobin.

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DECODE: PPHG is a risk factor
for CVD mortality
Hazard ratio for




<4.5 4.66.0 6.16.9 7.0 >11.0 10.111.0 7.810.0 6.67.7 3.16.5 3.0

FPG (mmol/L) 2hPG (mmol/L)

FPG, fasting plasma glucose; PG, plasma glucose

DECODE Study Group, European Diabetes Epidemiology
Group. Diabetes Care 2003;26:68896

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DECODE: PPHG is better correlated with
cardiovascular and all-cause mortality than FPG
Hazard ratio

FPG (mmol/l)

DECODE Study Group. Lancet 1999;354:617-21.

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PPG & 2hPG are associated with a greater
risk of CVD events and all-cause mortality
than FPG
CVD mortality All-cause mortality

CVD mortality end All-cause mortality nd

ar tr st) r tre )
lin ald te l inea d test
01 01 Wal
0.0 (A W 0.0
for for

Cardiovascular All-cause
events mortality

PPG, postprandial plasma glucose; 2hPG, 2h plasma glucose in oral glucose tolerance test; CVD, cardiovascular disease; FPG, fasting plasma glucose.
DECODE/DECODA adjusted for age, sex, cohorts, body mass index, systolic blood pressure, cholesterol, smoking. DECODA also adjusted for 2hPG (FPG model)
and FPG (2hPG model). In San Luigi Gonzaga, four glycemic parameters and A1c were analysed separately as individual predictors.
HR=1 (standard) for known diabetes (DECODE), <6.1 (FPG) and <7.8 mmol/l (2hPG) (DECODA), 3.9-7.2 (FPG) and <10 mmol/l (PPG) (San Luigi Gonzaga).
Figure modified from The DECODE study group. Diabetes Care 2003;26:688-696.
Figure created from Nakagami T, et al. Diabetologia 2004;47:385-94.
Figure created from Cavalot F, et al. Diabetes Care 2011;34:2237-43.

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PPG contributes to HbA1c
Relative contribution of PPG to HbA1c
PPG can occur even when overall metabolic 100
control appears to be adequate as
assessed by HbA1c1 80

The relative contribution of PPG to overall

glycaemia increases as HbA1c decreases1,2

Control of PPHG is an important 20

consideration for achieving recommended
HbA1c goals1 0

HbA1c sixtiles (%)

Target HbA1c will not be reached without bringing down postprandial hyperglycaemia
2011 Guideline For Management of Postmeal Glucose In Diabetes. Available at: http://www.idf.org/.
Figure modified from Woerle HJ, et al. Diab Res Clin Pract 2007;77:280-5.

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Emerging evidence associates mealtime
glucose spikes and risk of CVD and
DECODE, 1999 1
High 2-hour post-load blood glucose is
associated with increased risk of death,
independent of FPG
Pacific and Indian Ocean, 1999 2
Isolated 2-hour hyperglycemia doubles
the risk of mortality
Funagata Diabetes Study, 1999 3
IGT, but not IFG, is a risk factor for CVD
Whitehall, Paris, Helsinki Study, 1998 4
Men in upper 2.5% of 2-hour post-meal
glucose distribution had significantly
higher CHD mortality
The Rancho-Bernardo Study, 1998 5
2-hour post-challenge hyperglycemia
more than doubles the risk of fatal CVD
and heart disease in older adults
Diabetes Intervention Study, 1996 6
Post-meal, but not fasting glucose, is
associated with CHD
1. DECODE Study Group. Lancet 1999;354:61721. 2. Shaw JE et al. Diabetologia 1999;42:10504
3. Tominaga M et al. Diabetes Care 1999;22:9204. 4. Balkau B et al. Diabetes Care 1998;21:3607
5. Barrett-Connor E et al. Diabetes Care 1998;21:12369. 6. Hanefeld M et al. Diabetologia 1996;39:157783

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What drugs prevent the onset of T2DM?

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ESC/ EASD Guideline 2013

New ESC/ EASD Guideline 2013

ESC Essential Messages adapted from ESC Guideline on diabetes, pre-diabetes, and cardiovascular disease
(Eur Heart Journal 2013 doi: 10.1093/eurheartj/eht108)

Alpha-Glucosidase Inhibitors is one of the

pharmacotherapies that can delay
progression to DM in people with IGT
ESC Essential Messages, 2013

Page 22 RTD Pre Diabetes Glucobay

IDF consensus on type 2 diabetes

Acarbose is recommended
as a pharmacological option
to prevent the onset of type
2 diabetes when lifestyle
modification alone has not
achieved the desired weight
loss and/or improved
glucose tolerance goals

Alberti KGGM, et al. Diabet Med 2007;24:45163

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Chinese Prevention Study acarbose reduces the
risk of progression from IGT to type 2 diabetes

Reduction in the
risk of type 2
11.6 ~29% 77% 88% diabetes
Annual incidence

of diabetes (%)

Control Diet + exercise Metformin + Acarbose +
Diet + exercise Diet + exercise
p=0.0928 p=0.0002 p=0.0001
vs. control vs. control vs. control
Yang W, et al. Chin J Endocrinol Metab 2001;17:1316

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Glucobay has better efficacy than Metformin

Placebo (n=31)
HbA1c (%)

Metformin (n=31)

Glucobay (n=29)

Screening 0 6 12 18 24
Treatment Period (weeks)

Hoffmann J, Spengler M. Am J Med 1997;103:48390.

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Acarbose reduces PPHG
without acarbose
Intestinal glucose resorption

Without acarbose

Blood glucose
with acarbose

With acarbose Normal


0 1 2 3 4 0 1 2 3 4
Hours Hours

Zick R, Schnitger F. Mainz: Verlag Kircheim; 2001.

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Acarbose has favourable efficacy and tolerability
profiles in Asian patients with type 2 diabetes

China1 Taiwan2
(N=2,480) (N=1,558)

FBG reduction (mg/dL) 56.1 32.0

2h-PG reduction (mg/dL) 111.3 52.2
HbA1C reduction (%) 1.9 1.0

Very good/good efficacy

(% of patients) 90.1 46.0

Very good/good tolerability

(% of patients) 89.1 60.6

Very good/good acceptance

(% of patients) 87.1 63.4

1. Su S-O, et al. Chin J Endocrinol Metab 2006;22:6a15

2. Hung Y-J, et al. Clin Drug Invest 2006;26:55965

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Study to Prevent Non-insulin Dependent

Diabetes Mellitus (STOP-NIDDM)

Development of Cardiovascular
Cardiovascular risk2 Blood
diabetes1 risk 2

25% 49% Any cardiovascular 34%

Single New cases of
OGTT (p=0.0015) event hypertension
(p=0.03) (p=0.006)

36% Two 91% Myocardial

OGTTs infarction

Chiasson JL, et al. Lancet 2002;359:20727

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STOP-NIDDM and MeRIA provide positive
evidence for controlling PPHG with acarbose*
Relative risk reduction (%) (vs

IGT, impaired glucose tolerance; MI, myocardial infarction.

STOP-NIDDM, Study to Prevent Non-Insulin-Dependent Diabetes Mellitus.
MeRIA, Meta-analysis of Risk Improvement under Acarbose. *: Approved indications varies from country to country. Please refer your
P-value vs placebo (cox proportional hazards model). local prescribing information. Lifestyle intervention is the first and basic
Figure created from Chiasson JL, et al. JAMA 2003;290:486-94. component in the management of diabetes. Acarbose is not indicated
Figure created from Hanefeld M, et al. Eur Heart J 2004;25:10-6. for cardiovascular protection.

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STOP-NIDDM acarbose reduces
CV risk in individuals with IGT

Chiasson JL, et al. JAMA 2003;290:48694 NIDDM

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MeRIA7 acarbose reduces CV risk
in type 2 diabetes patients

Hanefeld M, et al. Eur Heart J 2004;25:106

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Glucobay has long term efficacy

11 5-year surveillance study


Plasma Glucose (mmol/L)

9 HbA1c 14.0
HbA1c (%)

7 2 h PP

6 8.4

0 1 2 3 4 5
Treatment Period (years)
1 mmol/L = 18.02 mg/dl)
Mertes G. Diab Res Clin Pract 2001;52:193204.

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Acarbose has a good safety profile
Long-term safety profile established1,2

Most adverse effects are mild-to-moderate gastrointestinal

side effects
No toxicity owing to low absorption (<2%)4

No risk of hypoglycaemia when used as monotherapy3,5

Few drugdrug interactions3,4

Not associated with weight gain, and may be responsible for a

modest decrease in weight
1. Mertes G. Diabetes Res Clin Pract 2001;52:193204 2. Holman RR, et al. Diabetes Care 1999;22:2904
3. Lebovitz HE. Diabetes Reviews 1998;6:13245 4. Laube H. Clin Drug Invest 2002;22:14156
5. Holstein A, et al. Exp Clin Endocrinol Diabetes 2003;111:40514
6. Van de Laar F, et al. Diabetes Care 2005;28:16675

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Acarbose the only therapy shown to significantly
reduce the incidence of CV events in a population
with IGT

GLUCOBAY: the only OAD approved

by POM (2011) for Pre Diabetes

Chiasson JL, et al. Lancet 2002;359:20727

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Thank you!

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