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Pioglitazone and Rosiglitazone Have Different Effects on Serum Lipoprotein Particle Concentrations and Sizes in Patients With Type 2 Diabetes and Dyslipidemia

¹ Department of Endocrinology and Metabolism, Veterans Affairs Hospital and Indiana University, Indianapolis, Indiana
² Department of Endocrinology and General Medicine, University of North Carolina, Chapel Hill, North Carolina
³ Department of Endocrinology, Metabolism and Diabetes, University of Miami, Miami, Florida
⁴ International Diabetes Center, Park Nicollet Institute, Minneapolis, Minnesota
⁵ Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana
⁶ Takeda Pharmaceuticals North America, Lincolnshire, Illinois
⁷ Takeda Global Research and Development, Lincolnshire, Illinois

Address correspondence and reprint requests to Meng H. Tan, MD, Lilly Research Laboratory, Eli Lilly and Company, Indianapolis, IN 46285. E-mail: tan_meng{at}lilly.com

OBJECTIVE—Associated with insulin resistance in type 2 diabetes are increased serum triglycerides, decreased HDL cholesterol, and a predominance of large VLDL, small LDL, and small HDL particles. The comparative effects of thiazolidinedione insulin sensitizers on serum lipoprotein particle concentrations and sizes in type 2 diabetes are not known. We studied the effects of pioglitazone (PIO) and rosiglitazone (ROSI) treatments on serum lipoprotein particle concentrations and sizes in type 2 diabetic patients with dyslipidemia.

RESEARCH DESIGN AND METHODS—This is a prospective, randomized, double-blind, multicenter, parallel-group study. After a 4-week placebo washout period, patients randomized to PIO (n = 369) were treated with 30 mg q.d. for 12 weeks followed by 45 mg q.d. for another 12 weeks, while patients randomized to ROSI (n = 366) were treated with 4 mg q.d. followed by 4 mg b.i.d. for the same intervals. Lipoprotein subclass particle concentrations and sizes were determined by proton nuclear magnetic resonance spectroscopy at baseline and end point (PIO [n = 333] and ROSI [n = 325] patients).

RESULTS—PIO treatment increased total VLDL particle concentration less than ROSI treatment and decreased VLDL particle size more than ROSI. PIO treatment reduced total LDL particle concentration, whereas ROSI treatment increased it. Both treatments increased LDL particle size, with PIO treatment having a greater effect. Whereas PIO treatment increased total HDL particle concentration and size, ROSI treatment decreased them; both increased HDL cholesterol levels.

CONCLUSIONS—PIO and ROSI treatments have different effects on serum lipoprotein subclass particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia.

Abbreviations: Apo, apolipoprotein • HOMA-IR, homeostasis model assessment of insulin resistance • IDL, intermediate-density lipoprotein • NMR, nuclear magnetic resonance • OAM, antihyperglycemic medication • PIO, pioglitazone • ROSI, rosiglitazone • TZD, thiazolidinedione

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