PPAR activation

& lipid metabolism

Diabetic dyslipidaemia

Lipid profiles and hyperinsulinaemia in newly diagnosed type 2 diabetic patients

Niskanen L et al. Diabetes Care 1998;21:1861-9

Type 2 diabetes Control p

HDL-C (mmol/L) 1.07 1.34 <0.05

Triglycerides (mmol/L) 2.41 1.60 <0.05

LDL-C (mmol/L) 4.49 4.17 NS

Total-C (mmol/L) 6.43 6.7 NS

Fasting insulin (mU/L) 24.8 15.4 0.003

Effects of pioglitazone vs gliclazide addition to metformin on dyslipidaemia

% change from baselineafter 2 yrs

Triglycerides HDLcholesterol

LDLcholesterol

TC / HDL ratio

-23

22

2

-7

7

-6-10

-30.00

-20.00

-10.00

0.00

10.00

20.00

30.00

p<0.001

p<0.001

p<0.001

p<0.001

-17

Pioglitazone + Metformin

Gliclazide + Metformin

Betteridge DJ, Verges B. Diabetologia 2005; 48: 2477-81

Changes in dyslipidaemic profile with TZDs

*p<0.05 vs baseline; † p<0.001 between treatment groups

Goldberg RB et al. Diabetes Care 2005; 28: 1547–1554Goldberg RB et al. Circulation 2005; 111: 1727–1728

-12,0

14,914,9

7,8

18,6

3,8

-15

-10

-5

0

5

10

15

20

25

30

Pioglitazone (n=363)

Rosiglitazone (n=356)

*

† *

Change from baseline to endpoint (%) after 24 weeks

† *

† *

Mean baseline mmol/LMean endpoint mmol/L

2.9 2.72.3 2.8

1.0 1.0 1.15 1.08

4.0 4.04.1 4.6

**

Triglycerides HDL-C Non-HDL-C

Sulfonylurea + TZD or metformin:Comparison of lipid and renal effects

Hanefeld M et al. Diabetes Care. 2004;27:141-7.

N = 639 with poorly controlled DM2

-20

-15

-10

-5

0

5

10

15

TG HDL-C TC:HDL-C LDL-C Alb:Cr

*

†

‡

†

†

*P = 0.008, †P < 0.001, ‡P = NS

Pioglitazone 15–45 mg + sulfonylurea Metformin 850–2550 mg + sulfonylurea

Change after 52

wks(%)

TZDs and metformin reduce risk of MICase-control study of insulin-sensitizing therapy and first MI in patients with type 2 diabetes

*Adjusted for age, sex, BMI, ACE inhibitor use, history of hypertension or hypercholesterolemia

Sauer WH et al. Am J Cardiol. 2006; 97:651-4.

MonotherapyMetformin

TZD

TZD + sulfonylurea

Metformin + sulfonylurea

Insulin-sensitizing drugs

Sulfonylureamonotherapy

P

0.01

0.03

0.04

0.19

Odds ratio for MI (95% CI)*

Combination therapy

Patients Controls

38 87

7 19

7 18

40 62

0 0.2 0.4 0.6 0.8 1.0 1.2

n