Having three or more metabolic risk factors raises diabetes risk in people with HIV
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Key takeaways:
- In REPRIEVE, incidence rates for new-onset diabetes were highest for people with HIV and three or more metabolic risk factors.
- Similar diabetes incidence rates were seen in the pitavastatin and placebo groups.
In adults living with HIV, those with three or more metabolic risk factors had a higher risk for developing new-onset diabetes than those without any risk factors, according to new findings from the REPRIEVE trial.
As Healio previously reported, REPRIEVE was a phase 3 randomized controlled trial where 7,731 adults aged 40 to 75 years with HIV, low to moderate risk for atherosclerotic cardiovascular disease (ASCVD) and no diabetes at baseline were randomly assigned to receive 4 mg pitavastatin or placebo once-daily. The trial was stopped at a median of 5.1 years of follow-up, with adults receiving pitavastatin having a lower risk for a major adverse CV event (MACE) compared with placebo (HR = 0.65; 95% CI, 0.48-0.9).
In a new analysis, published in published in the Annals of Internal Medicine, researchers found the risk for new-onset diabetes rose with the number of metabolic risk factors present among each participant at baseline, regardless of whether they were in the pitavastatin or placebo group.
“This is important as recent guidelines have expanded to recommend statin therapy for CVD prevention to all people with HIV with a traditional CVD risk score more than 5%, including many with normal LDL cholesterol levels,” Steven K. Grinspoon, MD, study chair for REPRIEVE and professor of medicine at Harvard Medical School, told Healio. “These data, showing effects on MACE in the overall REPRIEVE trial population — including in the limited group developing diabetes — reinforce the efficacy of statin therapy among people with HIV, suggesting an overall favorable risk-benefit profile.”
Diabetes rates tied to risk factors
During follow-up visits in REPRIEVE, participants self-reported new diagnoses of diabetes. Researchers confirmed the diagnoses in medical records. Metabolic risk factors at baseline included use of antihyperglycemic medications, prediabetes with a fasting glucose between 5.55 mmol/L and 6.99 mmol/L (100 mg/dL and 125 mg/dL), obesity, elevated waist circumference, low HDL cholesterol and high triglycerides.
There were 414 adults diagnosed with new-onset diabetes in the trial and 7,317 participants without diabetes. Of the participants, 65% with new-onset diabetes were deemed to have metabolic syndrome compared with 15% of those without diabetes. No diabetes risk factors were observed in 8% of those with new-onset diabetes vs. 29% without diabetes. Median ASCVD risk score was higher among adults who developed diabetes compared with those without diabetes (5% vs. 4.4%).
Diabetes incidence rates climbed as the number of metabolic risk factors increased for participants. Among adults receiving pitavastatin, those with three or more risk factors had a diabetes incidence rate of 3.24 per 100 person-years compared with a 0.34 per 100 person-years rate for people with no risk factors. For the placebo group, participants with three or more metabolic risk factors had a diabetes incidence rate of 2.66 per 100 person-years compared with a rate of 0.27 per 100 person-years for people with no risk factors.
Researchers observed racial-ethnic disparities in diabetes incidence rates. Adults located in South Asia had a higher diabetes incidence rate than those located in other regions. In a subanalysis restricted to people with high incomes, Black adults had higher diabetes incidence rates than white and Asian adults, both in the pitavastatin and placebo groups. Grinspoon said more studies are needed to examine the mechanisms behind these higher rates.
MACE rates lower with pitavastatin
Among adults diagnosed with new-onset diabetes during the trial, two receiving pitavastatin and six receiving placebo had primary MACE. The MACE incidence rate among those with diabetes was higher with placebo (12.4 per 1,000 person-years) than with pitavastatin (3.28 per 1,000 person-years).
Grinspoon said the study reveals people with HIV and metabolic risk factors tied to diabetes should lose weight and participate in lifestyle interventions to lower their diabetes risk.
“Implementation of such measures should be considered to prevent the development of diabetes in the large population of people with HIV at risk for CVD,” Grinspoon said. “Such measures to reduce the risk [for] diabetes will also benefit those beginning statin therapy.”
Grinspoon said future studies should examine the efficacy of weight loss interventions for reducing the risk for diabetes and CVD for people with HIV.
For more information:
Steven K. Grinspoon, MD, can be reached at sgrinspoon@mgh.harvard.edu.
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