Delaying complication in DM2 treatment

Type 2 diabetes: A true epidemic

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

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

DIABETES: A GROWING EPIDEMIC

Burden of morbidity and mortality in DM type 2

Burden of Morbidity and Mortality

UKPDS. Lancet 1998;352:837-53

Long-term Complications

MCIStrokeRetinopathy

Premature mortality

Diabetes deathsLife expectancy

27 patients10 patients23 patients

28 patients 5-7 years

UKPDS UKPDS

100 DM patients -diagnosed at age 55

151413121110

987654321

Years of Follow-

up

k

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®

hypoX-jsk-7-99

IGT Postprandial Hyperglycemia Type 2

DiabetesPhase 1 Type 2

DiabetesPhase 2

Type 2DiabetesPhase 3

- 12 - 10 - 6 - 2 0 2 6 10 14Years from diagnosis

Bet

a ce

ll fu

nctio

n (%

)Stages of type 2 Diabetes in relationship to Stages of type 2 Diabetes in relationship to

--cell functioncell function

25

0

50

75

100

Prediabetes Type 2 diabetes

Modifying disease progression through treatment

Diabetes duration (years)

Plasmaglucose(mg/dl)

–20 –10 0 10 20 30

126

100

Postprandial

Fasting

Insulin resistance

Insulin resistance

Insulin level

Adapted from Bergenstal RM, et al. Diabetes mellitus, carbohydrate metabolism and lipid disorders. In Endocrinology. 4th ed. 2001.

Microvascular complications

Macrovascular complications

Relativefunction

Obesity IGT Diabetes (Uncontrolled)

Prediabetes Type 2 diabetes

Microvascular complications

Macrovascular complicationsWhat should treatment aim to do?

Lowering the burden of insulin resistance may lead to β cell protection

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

Adding Actos ® early may lead to β 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%

Time from Randomisation (months)

36

406 (139)

0 6 12 16 24 30

N. at risk:2455 2351 2308 2265 22222397

0.10

0.05

0.04

0.03

0.01

0.0

0.02

Kaplan-Meier Event Rate

Placebo

Pioglitazone

(54 / 1215)

(35 / 1230)

-37 %

p-Value

0.41, 0.97

95 % CIHR

Pioglitazone vs Placebo 0.63 0.035

Pioglitazone’s effect on Acute Coronary Syndrome in patients with previous MI

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

Pioglitazone’s effect on recurrent stroke in patients with previous stroke

N at Risk:

Time from Randomisation (months)

984 952 926 903 877 849 132

Kaplan-Meier event rate

0.04

0.06

0.08

0.10

0.00

0.12

0 6 12 18 24 30 36

Placebo (51 / 498)

0.02

Pioglitazone (27 / 486)

0.0080.34, 0.85

0.53pioglitazone vs placebo

p value95% CIHR

- 47%

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

- 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)

• Combination with insulin (di Indonesia)

US FDA: NYHA II can be use with smaller starting dose (15 mg)

NYHA III – IV Not reccomended

• Pregnancy

US FDA : can be use in combination with insulin with adjusted dose

EMEA (Europe) : can be use in combination with insulin (Des. 2006)

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 β 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 β cell function

Delayed complication

• 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

Type of patients that will gain maximum benefit in adding Actos

Adding Pioglitazone Early to Delay Diabetes Complication

Thank you