Statin therapy alone does not appear to increase diabetes risk in patients with HIV and no other diabetes risk factors

Statin therapy is associated with risk for new-onset diabetes primarily in patients with HIV who have multiple metabolic risk factors, a recent study found.

Researchers used data from REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV), a global phase 3 trial of primary prevention in atherosclerotic cardiovascular disease (ASCVD) in HIV patients, to determine the contribution of known diabetes risk factors to excess risk for new-onset diabetes among patients taking pitavastatin versus placebo. The study included 7,731 patients ages 40 to 75 years who had HIV, low to moderate ASCVD risk, and no diabetes at study entry and were randomly assigned to receive pitavastatin, 4 mg/d, or placebo. New-onset diabetes was determined at each visit and was defined as a clinical diagnosis requiring medication. Incidence of new-onset diabetes was assessed in relation to predefined demographic and metabolic risk factors, stratified by treatment group, and the effect of pitavastatin on progression to diabetes was evaluated. The study results were published Oct. 8 by Annals of Internal Medicine.

Participants with at least three diabetes risk factors versus no risk factors had higher incidence of diabetes in each treatment group (incidence rate, 3.24 per 100 person-years vs. 0.34 per 100 person-years in the pitavastatin group and 2.66 per 100 person-years vs. 0.27 per 100 person-years in the placebo group). High body mass index, prediabetes, and components of the metabolic syndrome were strongly associated with new-onset diabetes in adjusted analyses (P<0.005 for all comparisons).

“Pitavastatin effects on DM [diabetes mellitus] differed by race and GBD [global burden of disease] region,” the authors wrote. “Still, clinically relevant absolute excess in risk with pitavastatin was seen only in those with significant clusters of DM risk factors at entry. Together these data suggest the importance of implementing comprehensive risk reduction strategies for PWH [people with HIV] with risk factors for DM, including dietary and exercise interventions.”

The authors also stressed that the general and statin-specific risk for diabetes is very low and probably not clinically relevant in patients with HIV who have normal body mass index and do not have prediabetes. “Of note, the overall effect of statin therapy to reduce MACE in REPRIEVE was highly significant, taking the increased risk for DM into account,” they wrote. “These findings may help inform the use of statins for the primary prevention of ASCVD among PWH, as well as the use of interventions to mitigate the risk for diabetes onset in higher-risk groups.”