The effect of simvastatin on triglyceride-rich lipoproteins in patients with type 2 diabetic dyslipidemia: a SILHOUETTE Trial Sub-study 

ABSTRACT

Objective: To determine if simvastatin effectively decreases the elevated levels of triglyceride (TG), TG-rich lipoproteins, and small, dense LDL particles, which are characteristic of diabetic dyslipidemia.

Research design and methods: We conducted a prespecified analysis from a double-blind, placebo-controlled, randomized, 6‐week crossover trial in patients with type 2 diabetes and low HDL‐C (< 40 mg/dL). Each patient was randomized to 1 of 6 possible treatment arms; each patient received simvastatin 80 mg, simvastatin 40 mg, and placebo over 3 periods. We used the validated vertical auto profile (VAP) method to directly assess TG-rich lipoproteins and LDL subclasses. We assessed the efficacy of simvastatin to improve the lipoprotein profile in adult men (71%) and women (29%) (n = 151) with stable type 2 diabetes (HbA_1C < 9%), LDL‐C > 100 mg/dL, HDL‐C < 40 mg/dL, and fasting TG level > 150 and < 700 mg/dL (median = 273 mg/dL).

† VAP is a trademark of Atherotech Inc., Birmingham, AL, USA

Main outcome measures: Percentage change from baseline in IDL and VLDL (TG-rich lipoproteins), LDL subclasses, and additional lipoproteins at the end of each 6‐week treatment interval; percentage of patients who reached NCEP ATP III non-HDL goal of < 130 mg/dL by the end of each 6‐week period.

Results: Both simvastatin 80 mg and 40 mg significantly reduced VLDL-C, VLDL₃, and IDL, as well as the four LDL subclasses measured with VAP, compared with placebo. Simvastatin 80 mg, compared with simvastatin 40 mg, provided additional efficacy. With simvastatin 80 mg, 77.2% of patients not at their non-HDL-C goal of < 130 mg/dL at study baseline reached goal, compared with 65.7% following simvastatin 40 mg treatment, and 2.2% following placebo.

Conclusions: Treatment with simvastatin effectively reduced the elevated levels of TG-rich lipoproteins and improved LDL composition in patients with type 2 diabetes. A large percentage of these patients attained the NCEP ATP III non-HDL‐C goal of < 130 mg/dL, which demonstrates the improvement of the atherogenic profile in these patients.

Key words: :

• Diabetes mellitus
• Efficacy
• Simvastatin
• Triglycerides

Notes

* Some of the information contained in this manuscript was presented at: American College of Cardiology (Orlando, FL, March 6-9, 2005). The primary efficacy and safety data, as well as additional details from this study, are published in Current Medical Research and Opinion, 2004;20:1087-94

† VAP is a trademark of Atherotech Inc., Birmingham, AL, USA