High Intensity Statin Therapy Increases Diabetes Risk – Renal and Urology News

Higher doses of statin therapy moderately increase the risk for new-onset diabetes, especially among individuals already at high risk, according to study findings published in Diabetes Endocrinology.

Although statins are widely used to reduce low-density lipoprotein cholesterol and the risk for cardiovascular events, previous findings from meta-analyses suggest a link between statin use and an increased risk for new-onset diabetes. However, these studies are limited by their reliance on summary data rather than individual participant data.

To clarify the relationship between statin therapy and diabetes risk, researchers conducted a meta-analysis of individual participant data from the Cholesterol Treatment Trialists’ (CTT) Collaboration. Inclusion criteria were double-blind, randomized controlled trials with at least 1000 participants and a mean scheduled follow-up of at least 2 years.

The researchers collected individual participant data on adverse events, treatments for diabetes, glycemic measurements, comorbidities, and laboratory results. Baseline diabetes was defined using various criteria, including history, medication use, and glucose levels.

The primary outcome was new-onset diabetes, which was defined according to glycated hemoglobin levels, glucose concentrations, diabetes-related adverse events, or glucose-lowering medication use after treatment assignment.

The analysis included 19 studies, of which 16 compared moderate intensity statin therapy with placebo, 2 compared high intensity statin therapy with placebo, and 4 compared more intense with less intense statin therapy. The population comprised 123,940 participants, of whom 18% had a history of diabetes at randomization and 2% met the baseline diabetes definition.

In studies of low intensity or moderate intensity statin therapy vs placebo among participants without diabetes at baseline (14 trials), statin vs placebo allocation was associated with an increased risk of developing diabetes (rate ratio [RR], 1.10; 95% CI, 1.04-1.16). The studies of high intensity statin therapy (2 trials) demonstrated an even greater increase in risk for diabetes (RR, 1.36; 95% CI, 1.25-1.48).

 The risk for new-onset diabetes increased by 10% among participants who received more intensive vs less intensive statin therapy (RR, 1.10; 95% CI, 1.02-1.18).  

The overall relative effects on new-onset diabetes remained consistent across various participant characteristics over time. Among participants with diabetes at baseline, worsening glycemia was associated with low intensity or moderate intensity statin vs placebo allocation (RR, 1.10; 95% CI, 1.06-1.14) and high intensity statin vs placebo allocation (RR, 1.24; 95% CI, 1.06-1.44).

The researchers noted larger relative effects on worsening glycemia during the earlier years of follow-up. Glucose concentration and glycated hemoglobin levels increased across different statin therapies.

Approximately 62% of new-onset diabetes cases were among those with baseline glycemic levels in the top quarter of the glycemia distribution.

Study limitations include the inclusion of trials not designed to assess the effect of statin therapy on new-onset diabetes, which could lead to overestimates of event rates, and the inability to assess the type of diabetes.

“People are most at risk of exceeding the diagnostic threshold for diabetes due to statin therapy if their glycaemic control is close to the threshold before treatment,” the researchers concluded. “The diabetes-related risks arising from the small changes in glycaemia resulting from statin therapy are greatly outweighed by the benefits of statins on major vascular events when the direct clinical consequences of these outcomes are taken into consideration.”

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Endocrinology Advisor