High-Intensity Statins Raise Diabetes Risk, While Fitness Strongly Protects Veterans, Finds Study
USA: Researchers have found in a new study of over 311,000 veterans with dyslipidemia that high-intensity statin therapy increased the risk of type 2 diabetes by 23% compared with low-intensity treatment, with risk rising further alongside higher BMI. Greater cardiorespiratory fitness significantly reduces the risk of diabetes, with the fittest individuals showing a 57% lower risk regardless of the statin intensity.
The large nationwide analysis, which was published in the Mayo Clinic Proceedings by Peter Kokkinos from the Veterans Affairs Medical Center, Washington, DC, and colleagues, provides new insights into how statin dosage, cardiorespiratory fitness (CRF), and body weight interact to influence the likelihood of developing type 2 diabetes (T2DM). While statins remain essential for lowering cardiovascular risk, the study suggests that the intensity of statin therapy and individual lifestyle-related factors may play a crucial role in shaping long-term metabolic outcomes.
The researchers evaluated a cohort of 311,269 veterans with dyslipidemia who had been taking statins for at least six months and had no prior history of diabetes when starting treatment. The average age of the cohort was 60.8 years. All participants had undergone a standardized treadmill exercise test between October 1999 and September 2020; individuals showing evidence of ischemia were excluded from the analysis.
Participants were categorized by statin intensity (low vs. high), body mass index (across four groups), and CRF levels, which were divided into five age- and gender-specific categories based on peak metabolic equivalents (METs) achieved during the exercise test.
The study led to the following notable findings:
- Over a median follow-up of almost 11 years, 56,994 participants developed type 2 diabetes, with an incidence rate of 16.7 cases per 1,000 person-years.
- High-intensity statin therapy was linked to a 23% higher risk of developing diabetes compared with low-intensity statin use.
- Diabetes risk increased substantially when high-intensity statins were combined with higher BMI.
- Obese individuals on high-intensity statins had a more than fourfold increased risk compared with normal-weight individuals on low-intensity statins.
- Cardiorespiratory fitness emerged as a strong protective factor against diabetes.
- Participants achieving 8.4 METs or higher showed an approximately 30% to 60% reduction in diabetes risk, regardless of BMI or statin intensity.
- Least-fit individuals on high-intensity statins had a 21% higher risk of diabetes compared with the least-fit individuals on low-intensity statins.
- Highly fit individuals on high-intensity statins experienced nearly a 50% reduction in diabetes risk.
The authors conclude that while high-intensity statin therapy is linked to a greater likelihood of developing type 2 diabetes, lifestyle factors—especially CRF and weight—can significantly modify this risk. They emphasize that promoting physical fitness and weight management among patients prescribed high-intensity statins may help counterbalance the heightened metabolic risk.
Reference:
Kokkinos P, Faselis C, Pittaras A, Samuel IBH, Cadenas-Sánchez C, Nylen E, Lavie C, Franklin B, Malin SK, Murphy R, Myers J. Diabetes Incidence According to Statin Intensity Regimen, Body Mass Index, and Cardiorespiratory Fitness. Mayo Clin Proc. 2025 Nov;100(11):1908-1920. doi: 10.1016/j.mayocp.2025.06.004. Epub 2025 Oct 1. PMID: 41031997.
Next Story