Effects of Pitavastatin on Insulin Sensitivity and Liver Fat: A Randomized Clinical Trial

Context: 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are widely prescribed. Statins may have important metabolic effects on insulin sensitivity and liver fat, but limited studies have assessed these effects by using euglycemic hyperinsulinemic clamp, stable isotopes, and H-1 magnetic resonance spectroscopy (MRS) for liver fat quantification. Objective: To study the effects of pitavastatin on hepatic fat and insulin sensitivity. Design: Six-month, double-blind, randomized, placebo-controlled trial. Setting: Academic clinical research center in Boston, Massachusetts. Participants: Overweight, insulin-resistant men aged 40 to 65 years who had not received statin therapy for >= 1 year. Interventions: Pitavastatin 4 mg or placebo daily. Outcome: The primary endpoints were changes in insulin sensitivity measured by euglycemic hyperinsulinemic clamp and liver fat measured by H-1 MRS. Results: Pitavastatin showed no effect on endogenous glucose production (Delta Ra glucose 0.07 +/- 0.07 vs 0.04 +/- 0.07 mg/kg/min, pitavastatin vs placebo, P = 0.76) or insulin-stimulated glucose uptake during "low dose" (Delta M0.1 +/- 0.1 vs -0.3 +/- 0.2 mg/kg/min, P = 0.11) and "high dose" (Delta M -0.5 +/- 0.3 vs -0.7 +/- 0.4 mg/kg/min, P = 0.70) euglycemic hyperinsulinemic clamps. There was also no effect of pitavastatin on fasting glucose, HbA1c, and 2-hour glucose after 75-g glucose challenge. There was also no change in liver fat fraction (-1 +/- 6 1 vs -0 +/- 1%, P = 0.56). Conclusion: Compared with placebo, pitavastatin did not affect hepatic or whole-body insulin sensitivity, and it did not reduce liver fat.