Efficacy of Pitavastatin, a New HMG-CoA Reductase Inhibitor, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes

Type 2 diabetes is one of the risk factors for macrovascular disease. Treatment of hypercholesterolemia is important in patients with type 2 diabetes to prevent macrovascular disease. The 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are key drugs to lower the cholesterol level not only in nondiabetic patients but also in patients with type 2 diabetes. However, some statins might worsen glycemic control (1) whereas some of them might be neutral (2) or improve glycemic control (3), and their effects on glucose metabolism are controversial. Pitavastatin, an HMG-CoA reductase inhibitor, has been available in Japan since 2003 (4) and the Republic of Korea since 2005, and its effect on glucose metabolism in diabetic patients remains unknown. Since safe use of statins is important for patients, we evaluated the effects of pitavastatin on lipid and glucose metabolism in this study.

A total of 79 type 2 diabetic patients (47 men and 32 women; mean age ± SD 61.7 ± 12.1 years; BMI 26.7 ± 4.2 kg/m²) with hypercholesterolemia who had never been treated with statins and attended one of five outpatient diabetic clinics were enrolled. Informed consent was obtained from all subjects. This study was designed as an 8-week intervention period with new administration of pitavastatin (1 or 2 mg/day). Fasting plasma glucose, HbA_1c, LDL cholesterol, HDL cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl-transferase, and creatine phosphokinase levels were measured both before and after 8 weeks of pitavastatin treatment. Differences in these parameters pre- and posttreatment were analyzed using Wilcoxon’s matched-pair signed-rank test.

Pitavastatin treatment resulted in a significant decrease in LDL cholesterol levels (from 4.28 ± 0.69 to 2.70 ± 1.03 mmol/l, P < 0.0001) and triglyceride levels (from 1.71 ± 0.76 to 1.54 ± 1.09 mmol/l, P < 0.0001), whereas the change in HDL cholesterol levels did not reach statistical significance (from 1.29 ± 0.32 to 1.33 ± 0.33 mmol/l, P = 0.055). Concerning glycemic control, changes in fasting plasma glucose levels (from 8.20 ± 2.71 to 8.27 ± 2.10 mmol/l) and HbA_1c levels (from 7.25 ± 1.60 to 7.27 ± 1.47%) were not statistically significant. Changes in other available parameters were also not statistically significant. No subject terminated the trial because of adverse events.

Our results showed that pitavastatin is a potent agent for lowering LDL cholesterol level and that it does not affect glycemic control in patients with diabetes. Although statins have been widely prescribed all over the world and are regarded as the first choice for hypercholesterolemia, physicians must pay attention to the adverse effects of these agents, e.g., myotoxicity, liver dysfunction, and worsened glycemic control, which might be related to the cytochrome P450–mediated metabolic pathway (4,5). The results in this study are an important observation for patients with diabetes and are consistent with another report that pitavastatin, which is metabolized with little involvement of cytochrome P450 isoenzymes (4), did not show these major adverse effects (6). Because pitavastatin has been marketed for only a few years, further studies with a greater number of subjects and a longer duration are needed to establish the safety of this agent.

In conclusion, pitavastatin is effective in lowering LDL cholesterol and triglyceride levels without affecting glycemic control in patients with diabetes. We believe that this agent must also help prevent the development of macrovascular disease in diabetic patients, as has been seen with other statins, but this still requires confirmation in a controlled clinical trial.