Rosuvastatin Worsens Insulin Resistance in HIV-Infected Adults on Antiretroviral Therapy

Abstract

Background: Statins are associated with increased diabetes risk in large, human immunodeficiency virus (HIV)-uninfected cohorts; the impact of statins on insulin resistance or diabetes in HIV-infected persons has not been assessed within a randomized controlled study.

Methods: HIV-infected participants on stable antiretroviral therapy with a low-density lipoprotein cholesterol level of ≤130 mg/dL and heightened immune activation or inflammation were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks. Fasting serum glucose, insulin, and hemoglobin A1C (HgbA1C) were measured; insulin resistance was estimated by calculating the homeostatic model assessment of insulin resistance (HOMA-IR); and a 2-hour oral glucose tolerance test was administered.

Results: Seventy-two participants were randomized to rosuvastatin therapy and 75 to placebo. Increases in fasting glucose were observed within both groups but were not different between study arms (P = .115); changes in glucose tolerance and HgbA1C did not differ between study arms (P = .920 and P = .650, respectively). Criteria for diabetes were met by 1 participant in the rosuvastatin and 3 in the placebo arm by week 96. Compared with placebo, rosuvastatin therapy was associated with significantly greater increases in insulin and HOMA-IR (P = .008 and P = .004, respectively).

Conclusions: We detected a significant worsening in insulin resistance and an increase in the proportion of participants with impaired fasting glucose but not a clinical diagnosis of diabetes in the rosuvastatin arm. Our findings suggest that prescription of statin therapy should be accompanied by a careful consideration of the risks and benefits, particularly in patients with lower cardiovascular disease risk.

Clinical trials registration: NCT01218802.

Keywords: HOMA-IR; glucose metabolism; inflammation; insulin resistance; statin.

Figure 1.

Relative mean changes from study entry to weeks 24, 48, and 96. The rosuvastatin arm is shown by the dotted line and circles, and the placebo arm by the dashed line and squares. The error bars represent the 95% confidence intervals and the P value compares the relative change between rosuvastatin and placebo. A, Change in fasting glucose; B, change in glucose 2-hours following an oral glucose load; C, change in hemoglobin A1C; D, change in fasting insulin; and E, change in fasting homeostatic model assessment of insulin resistance. Abbreviation: HOMA-IR, homeostatic model assessment of insulin resistance.