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 1H 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 1H MRS.

RESULTS

Pitavastatin showed no effect on endogenous glucose production (ΔRa 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" (ΔM 0.1 ± 0.1 vs -0.3 ± 0.2 mg/kg/min, P = 0.11) and "high dose" (ΔM -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 ± 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.