Bridging of Insulin Resisten and CV Protection - The Role of Pioglitozone
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Transcript of Bridging of Insulin Resisten and CV Protection - The Role of Pioglitozone
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Delaying complication in DM2 treatment
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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
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DIABETES: A GROWING EPIDEMIC
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Burden of morbidity and mortality in DM type 2
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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
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k
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Delaying DM2 complication
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Early and Intensive glycemic control delays diabetes complication
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Early and Intensive glycemic control delays diabetes complication
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Current management approach often fails to achieve glycaemic target
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Adding Actos early helps achieve long-term sustained glycaemic control
Hanefeld M, et al Curr Med Res Opin 2006:22;1211-1215
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Another benefit of early use of Actos®
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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
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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?
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Lowering the burden of insulin resistance may lead to β cell protection
Hanefeld M, et al Curr Med Res Opin 2006:22;1211-1215
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Adding Actos ® early may lead to β cell
protection
Hanefeld M, et al Curr Med Res Opin 2006:22;1211-1215
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Adding Actos® early delaying complication
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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
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RR
19%
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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
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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
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- 54%
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Adding Pioglitazone Early to Delay Diabetes
Complication
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Actos® safety and tolerability
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Weight gain
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Weight gain
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Heart Failure
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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)
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Message to take home
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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
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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
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Type of patients that will gain maximum benefit in adding Actos
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Adding Pioglitazone Early to Delay Diabetes Complication
Thank you