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Dual Inhibition of Two Sources of Cholesterol: Absorption and Production in Patients with Type 2 Diabetes

Results of a Clinical Trial with Ezetimibe Coadministered with Simvastatin vs. Simvastatin Alone

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Study Design• Design

– Multicenter, double-blind, randomized, 24-week study following a 6-week run-in period during which all patients received simvastatin 20 mg/day

• Treatment groups– Ezetimibe + Simvastatin* 20 mg once daily (n=104)– Simvastatin 40 mg once daily (n=110)

• Selected entry criteria– Age 30 to 75 years– Type 2 diabetes mellitus (HbA1c 9.0%)– Prior treatment with thiazolidinediones– LDL-C 100 mg/dl (2.58 mmol/L) prior to initiation

of simvastatin therapy

*Eze+Simva in this presentation.

Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

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Endpoints

• Primary– Percent change from baseline in plasma LDL-C

• Key secondary– Percentage of patients reaching target LDL-C levels

of <100 mg/dl (<2.58 mmol/L)– Percent change from baseline in other lipoproteins, lipids,

and apolipoproteins

Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

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Baseline Characteristics

Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

Eze+Simva 20 mg

(n=104)

Simvastatin40 mg

(n=110)

Age Mean(years) Range

5835–80

5837–78

Gender Male (% of patients) Female

60 40

55 45

Race White(% of patients) Hispanic

BlackOther

53 24 15 8

55 27 12 6

Lipids Mean LDL-C (mg/dl) 94 91Mean total cholesterol (mg/dl) 172 168Mean HDL-C (mg/dl) 47 49Median triglycerides (mg/dl) 150 152

Diabetes Mean BMI (kg/m2)parameters Mean HbA1c (%)

Mean fasting serum glucose (mg/dl)Mean fasting serum insulin (µlU/ml)

33 7142 15

34 7147 14

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LDL-C Reduction from Simvastatin Baseline

*p<0.001 vs. simvastatin

Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

Mea

n %

ch

ang

e fr

om

b

asel

ine

at 2

4 w

eeks

0

–10

–15

–20

–5

Simvastatin40 mg

(n=110)

–0.3

Eze+Simva 20 mg

(n=104)

–21*

–25

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Percentage of Patients Who Achieved LDL-C Goal of <100 mg/dl

% P

atie

nts

**

80

10

Simvastatin40 mg(n=33)

39

Eze+Simva 20 mg

(n=37)

76*

0

20

30

40

50

60

70

*p<0.001 vs. simvastatin**Subgroup of patients who were not at goal at randomization (baseline) following six weeks of treatment with simvastatin 20 mg/day

Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

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Reductions in Other Lipids fromSimvastatin Baseline

*p<0.001 vs. simvastatin

Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

LS

mea

n %

ch

ang

e fr

om

bas

elin

e

0

–10

–15

–20

–5

–25Eze+Simva 20 mg (n=104)Simvastatin 40 mg (n=110)

Totalcholesterol

–2

–15*

Apolipoprotein B

–2

–14*

Non–HDL-C

–2

–20*

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*Based on investigator assessment of dipstick results**Asymptomatic and transient

Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

Adverse Events of Interest% of Patients

Eze+Simva 20 mg

(n=104)

Simvastatin40 mg

(n=110)

ClinicalAnemiaEdemaWeight gainMyopathy

1510

4500

LaboratoryIncreased HbA1c

Increased fasting blood sugarProteinuria*ALT 3 ULN (consecutive)AST 3 ULN (consecutive)CPK 10 ULN

11010

1**

320

<100

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• Dual Inhibition of cholesterol absorption and production with Eze+Simva 20 mg was more effective than doubling the dose of simvastatin to 40 mg

Greater LDL-C reduction (p<0.001)

More patients achieved LDL-C goal (p<0.001)

Greater improvements in overall lipid profile (total cholesterol, apolipoprotein B, non–HDL-C)

Similar effects on HDL-C and triglycerides

Similar safety and tolerability profile

Conclusions

Adapted from Gaudiani L et al. Poster presentation at the 53rd ACC, March 7–10, 2004.

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References

• Please refer to notes page.

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Dual Inhibition of Two Sources of Cholesterol: Absorption and Production in Patients with Type 2 Diabetes

Before prescribing, please consult the manufacturers’ prescribing information.

MSP does not recommend the use of any product in any different manner than as described in the prescribing information.

Copyright © 2004 MSP Singapore Company, LLC.All rights reserved. 5-05 EZT 2004-W-6143-SS Printed in USA