Delaying complication in DM2

treatment

Type 2 diabetes: A true epidemic

By the year 2030, 350 million people will have
type 2 diabetes

Wild et al. Diabetes Care 2004;27:1047-53

DIABETES: A GROWING EPIDEMIC

Burden of morbidity and

mortality in DM type 2

Burden of Morbidity and Mortality

Years of
Followup

UKPDS
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1

100 DM patients diagnosed at age 55

Long-term Complications
MCI
Stroke
Retinopathy

27 patients
10 patients
23 patients

Premature mortality
Diabetes deaths
Life expectancy

28 patients
5-7 years

UKPDS. Lancet 1998;352:837-53

Delaying DM2 complication

Early and Intensive glycemic control delays

diabetes complication

Early and Intensive glycemic control delays

diabetes complication

Current management approach often fails to

achieve glycaemic target

Adding Actos early helps achieve long-term

sustained glycaemic control

Hanefeld M, et al Curr Med Res Opin 2006:22;1211-1215

Another benefit of early use of

Actos

Stages of type 2 Diabetes in relationship to

100
-cell function

Beta cell function (%)

75

50

IGT

Postprandial
Hyperglycemia

25

Type 2
Diabetes
Phase 1

Type 2
Diabetes
Phase 3

Type 2
Diabetes
Phase 2

0
- 12 - 10

-6

-2

Years
from diagnosis
hypoX-jsk-7-99

10

14

Modifying disease progression through

treatment
IGT

Obesity

126

(Uncontrolled)

Prediabetes

Type 2 diabetes

Prediabetes

Macrovascular
Typecomplications
2 diabetes

What should treatment

aim to do?

Plasma
glucose
(mg/dl)

Diabetes

Microvascular complications
Macrovascular complications
Microvascular complications

Postprandial
Fasting

Insulin
resistance
Relative
function

100

Insulin level

10
10
20lipid disorders.
30 In Endocrinology. 4th ed.
Diabetes
duration
(years)RM, 20
Adapted
from Bergenstal
et al. Diabetes
mellitus, carbohydrate
metabolism
and
0
2001.

Lowering the burden of insulin resistance

may lead to cell protection

Hanefeld M, et al Curr Med Res Opin 2006:22;1211-1215

Adding Actos early may lead to cell

protection

Hanefeld M, et al Curr Med Res Opin 2006:22;1211-1215

Adding Actos early delaying

complication

Time to permanent insulin use was lower in

Actos

Time to failure of glycemic control (HbA1c 8%, progression to permanent insulin use) in patients
with DM2 treated in pioglitazone or glibenclamide In addition to existing metformin therapy
Hanefeld M, et al Curr Med Res Opin 2006:22;1211-1215

RR
19%

Pioglitazones effect on Acute Coronary Syndrome

in patients with previous MI
Kaplan-Meier
Event Rate

Erdmann E. et al. JACC 2007; 49: 1772-1780

0.10
Pioglitazone (35 / 1230)

0.05

Placebo

(54 / 1215)

-37 %

0.04
0.03
0.02
0.01

HR

0.0
N. at risk: 2455

Pioglitazone vs Placebo

95 % CI p-Value

0.63 0.41, 0.97 0.035

2397

2351

2308

2265

2222

406 (139)

12

16

24

30

36

Time from Randomisation (months)

Pioglitazones effect on recurrent stroke

in patients with previous stroke
Kaplan-Meier event rate
0.12
Pioglitazone (27 / 486)
Placebo
(51 / 498)

0.10

- 47%

0.08
0.06
0.04
0.02
pioglitazone vs placebo

0.00

N at Risk: 984

952

926

903

877

12

18

24

HR

95% CI

p value

0.53

0.34,
0.85

0.008

849

30

Time from Randomisation (months)

Wilcox R et al. STROKE 2007; 38: 865-873

132

36

- 54%

Adding Pioglitazone
Early to Delay Diabetes
Complication

Actos safety and tolerability

Weight gain

Weight gain

Heart Failure

Actos contraindication

Hypersensitive with pioglitazone

Liver disfunction
Not recommended if : SGPT > 2,5 x ULN (upper level normal)

Heart Failure (NYHA I IV)

US FDA: NYHA II

can be use with smaller starting dose (15 mg)

NYHA III IV Not reccomended

Combination with insulin (di Indonesia)

US FDA : can be use in combination with insulin with adjusted dose
EMEA (Europe) : can be use in combination with insulin (Des. 2006)

Pregnancy

Message to take home

Message to take home

DM2 caused burden morbidity and mortality with total
mortality and major non fatal CV events 3 times more
likely compare with non diabetic population
Current management approach often fails to achieve
glycaemic target
Early course glycaemic control with sustaining durability
is key important factor to delay DM complication
Deterioration of cell function is correlating with DM2
progressivity

Message to take home

For Metformin failure patients (HbA1c > 7 %), Adding
Actos early will provide:
Sustained glycaemic control
Improving insulin sensitivity , preserving cell function

Adding Actos to metformin failure prove to delay

progression to permanent insulin use
For long-term use Actos safe, does not increase
mortality due to CV events

Delayed
complication

Type of patients that will gain maximum benefit in

adding Actos

Adding Pioglitazone Early to

Delay Diabetes Complication

Thank you