REPRIEVE Team Publishes Analysis of Incidence of Diabetes and Risk Factors

The REPRIEVE study (Randomized Trial to Prevent Vascular Events in HIV) led to new recommendations (known as guidelines) for the use of statins (cholesterol-lowering medicine) among people living with HIV who are at low-to-moderate risk for atherosclerotic cardiovascular disease (also known as heart disease). These findings have been game changing, but it is also important to note that statins have been associated with the development of diabetes. “Diabetes Risk Factors in People With HIV Receiving Pitavastatin Versus Placebo for Cardiovascular Disease Prevention: A Randomized Trial” was recently published in the Annals of Medicine. This publication sought to address the fact that little is known about how people living with HIV develop diabetes or how statins might lead diabetes to among this population. The objective of this research was to understand the role of known diabetes risk factors (including being overweight, having higher blood sugar levels at the time of study entry, etc.) in increasing the likelihood that people living with HIV and taking pitavastatin in REPRIEVE would develop diabetes.

REPRIEVE was a phase 3, global, multicenter trial with a median of 5.6 years of follow-up and included 7,731 people living with HIV between the ages of 40 to 75 who had low-to-moderate heart disease risk and did not have diabetes at study entry. Participants were divided equally and randomly to either receive pitavastatin (4 mg daily) or placebo. Participants were screened for diabetes at each study visit. They were classified as having diabetes if they received a clinical diagnosis in their medical record by a provider or they started taking diabetes medication. The incidence of new-onset diabetes was assessed in relation to predefined demographic and metabolic risk factors (e.g., obesity, evidence of insulin resistance, etc.), stratified by treatment group and the effects were determined of taking pitavastatin on new diabetes cases in key subgroups.

The study found that participants with at least three risk factors for diabetes (compared to no risk factors) had an increased risk of developing diabetes in both treatment groups (the incidence rate was 3.24 per 100 person-years vs. 0.34 per 100 person-years among participants receiving pitavastatin and 2.66 per 100 person-years vs. 0.27 per 100 person-years in participants receiving placebo). The incidence of diabetes was highest in South Asia. Analyses showed that high body mass index, prediabetes, and metabolic syndrome components were strongly associated with new-onset diabetes (all P< 0.005).

This study has several limitations, including that pitavastatin was the only statin assessed and that diabetes was assessed clinically. Because a clinically significant effect of pitavastatin on diabetes was seen primarily among those with multiple risk factors at study entry, strategies targeting key metabolic risk factors, like obesity and prediabetes, may help protect against diabetes among people living with HIV.

Until now, it was unclear why statins were associated with the development of diabetes and who was most at risk. This publication sheds light on the fact that diabetes was more common in those who were already at the highest risk of getting it and demonstrated that for participants with no risk, the statin used in this study did not cause diabetes.

Kathleen V. Fitch, Markella V. Zanni, Jennifer Manne-Goehler, et al. Diabetes Risk Factors in People With HIV Receiving Pitavastatin Versus Placebo for Cardiovascular Disease Prevention: A Randomized Trial. Ann Intern Med. [Epub 8 October 2024]. doi:10.7326/ANNALS-24-00944