1 A Comparison of Lipid and Glycemic Effects of Pioglitazone and Rosiglitazone in Patients With Type 2 Diabetes and Dyslipidemia Diabetes Care 28:1547–1554, 2005 R2 박정은

2 Background Type 2 diabetes –relative insulin insufficiency + insulin resistance The dyslipidemia associated with insulin resistance and type 2 diabetes –TG ↑, HDL cholesterol↓ –LDL cholesterol : not increased, small, dense, more atherogeic Increased coronary heart disease

3 Background Thiazolidinedione –Glucose-lowering effect + alter lipid/lipoprotein metabolism –Pioglitazone, rosiglitazone Pioglitazone has differential effects on lipid parameters in patients with type 2 diabetes when compared with rosiglitazone. –Retrospective chart review –Concomitant glucose-lowering and lipid-lowering therapies

4 Objects The lipid and glycemic effects of pioglitazone and rosiglitazone. Pioglitazone has greater triglyceride-lowering effects than rosiglitazone. Multicenter, prospective, randomized, double-blind, parallel group comparison of maximally effective monotherapy doses of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia No concomitant glucose-lowering or lipid-lowering therapies.

5 Methods Subjects –> 35 years of age –Type 2 diabetes –Fasting TG levels : ≥ 150 mg/dL, ≤ 600 mg/dL –Fasting LDL cholesterol : < 130 mg/dL –C-peptide ≥ 1ng/dL –HgA1c : ≥ 7%, ≤ 11% ( no previous OHA ) ≥ 7%, ≤ 9.5% ( previous OHA monotherapy )

6 Methods Subjects : exclusion –insulin –systemic glucocorticoid therapy –combination OHA therapy any lipid- lowering agent –any weight loss agent –known allergy to TZD –Cr ≥ 2 mg/dL –2+ dipstick proteinuria –AST/ALT ↑(1.5 times) –Anemia –NYHA class III,IV –CVD

7 Study design Study design Enrolled patients Current OHA stop Oral placebo 30mg pioglitazone Once daily 4mg rosiglitazone once daily 45mg pioglitazone Once daily 4mg rosiglitazone twice daily 4 weeks 12 weeks

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15 Discussion The mechanism by which these agents exert differential effects on the lipid profile are not clearly understood. Risk factors for CVD –↑LDL cholesterol, total cholesterol, and triglycerides –↓HDL cholesterol –Primary target : lowering LDL cholesterol

16 Discussion Dyslipidemia of diabetes –TG ↑, HDL cholesterol↓, near normal LDL cholesterol –Insulin resistance : qualitative changes in the composition of LDL cholesterol –LDL particles : decrease in particle size and a greater density of each particle –Increase in TG levels in type 2 diabetes is in part responsible for these atherogenic changes in the LDL profile

17 Discussion Pioglitazone and rosiglitazone differed significantly with opposing effects on triglycerides. Pioglitazone : small, dense → larger, more buoyant LDL : decreased particle concentration Rosiglitazone : ↑LDL particle size, TG levels and LDL particle numbers

18 Discussion Differences in the lipid effects between pioglitazone and rosiglitazone 1.The shift toward larger LDL particles observed with rosiglitazone therapy cannot be due to effects on TG levels. 2.The increase in LDL by pioglitazone – Increased in particle size – Slightly decreased number of LDL particles 3.The increase in LDL by rosiglitazone – Both increased in size and number of LDL

19 Conclusion Pioglitazone and rosiglitazone exert different effects on plasma lipids. Pioglitazone is associated with significant improvements versus rosiglitazone in TG, HDL cholesterol, non-HDL cholesterol, and LDL particle concentrations and LDL particle size. –despite similar effects on glycemic control and surrogate measures of insulin resistance –Whether these differences in lipid effects translate into differences for the risk of CVD is not clear.