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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02290106.

Figures

Figure 1.

CONSORT flow diagram.

Figure 2.

Box and whisker plots showing change from baseline in (A) LDL-C, (B) low-dose clamp M, (C) high-dose clamp M, (D) hepatic fat fraction, (E) low-dose clamp M adjusted for insulin, and (F) high-dose clamp M adjusted for insulin. Data are presented as median (line), 25th and 75th percentiles (box), extremes (whiskers), and outliers (dots). M is insulin-stimulated glucose uptake.

Figure 3.

(A) Baseline and (B) final visit plasma glucose (diamonds) and insulin (triangles, dotted line) concentrations, and (C) baseline and (D) final visit glucose infusion rates during low-dose (min 0 to 120) and high-dose (min 120 to 240) hyperinsulinemic euglycemic clamp. Data are represented as means and SEM (bars). GIR, glucose infusion rate.