Statins linked to slight diabetes risk but benefits outweigh the concerns

By Dr. Chinta SidharthanReviewed by Susha Cheriyedath, M.Sc.Mar 28 2024

In a recent study published in The Lancet Diabetes & Endocrinology, a large collaborative team of researchers investigated the factors associated with the increased risk of diabetes due to statin use, such as the types of individuals or populations that are at greater diabetes risk due to statin therapy, at what point after beginning statin therapy does the risk increase, and whether the use of statins has an impact on the glycemic control of known diabetes patients.

Study: Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis. Image Credit: Fahroni / Shutterstock

Background

One of the leading causes of mortality across the world is cardiovascular disease, with low-density-lipoprotein (LDL) cholesterol being the major risk factor for atherosclerotic cardiovascular disease. The risk of atherosclerosis also increases significantly in diabetic patients. Treatment with statins such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor is believed to decrease the incidence of ischemic stroke and myocardial infarction by one-fourth for a reduction of 1 mmol/L LDL cholesterol reduction.

However, findings from recent meta-analyses have indicated that standard regimens of statin therapy are linked to a 10% increase in new-onset diabetes risk, as compared to usual care for hypercholesteremia or placebo. The risk of new-onset diabetes was also found to be higher with more intense regimens of statin therapy. However, aspects of this association between statin use and diabetes risk, such as the populations at greater risk and the impact of statin use on individuals already diagnosed with diabetes, remain unclear.

About the study

In the present study, the researchers obtained information on adverse events related to diabetes, diabetes treatments, and records of glycemia measurements from participants registered in the Cholesterol Treatment Trialists’ Collaboration, which consisted of double-blinded, long-term, randomized controlled trials evaluating statin therapy.

This study included statin therapy trials if they had a minimum of a thousand participants with a mean follow-up period of two years. Furthermore, the only differences mandated in the protocol of these trials had to be in the administration of statin therapy or placebo or the intensity of statin therapy. The individual participant data, which also included information on comorbidities, anthropometric measurements, and laboratory results for blood glucose tests, was used for a meta-analysis.

The adverse events related to diabetes that were considered in the analysis included a diagnosis of diabetes, complications related to diabetes, such as glucose control and ketosis, or any other complications specific to diabetes. The medications for lowering glucose levels were identified from the prescription information using a standard drug dictionary, and fasting status was used to categorize the glucose concentrations.

A history of diabetes, the occurrence of any diabetes-related adverse event, fasting blood glucose levels of 7 mmol/L or above, or the use of medications to lower blood glucose before the registration or assignment of the participant to the trial was used to define baseline diabetes. In those without baseline diabetes, the occurrence of any adverse event related to diabetes, a higher than the standard cut-off of blood glucose, or the use of any medication to lower blood glucose levels after the commencement of the trial were considered as new-onset diabetes diagnoses.

Results

The study found that statin use was indeed linked to an increase in new-onset diabetes, although the association was moderate and dose-dependent. Furthermore, while a slight increase in glycemia was observed after statin treatment, most of the diagnoses for new-onset diabetes were in individuals whose baseline glycemic markers were already quite close to the threshold for diagnosing diabetes.

The potential increase in cardiovascular disease risk that could occur due to the marginal increase in glycemia was accounted for in the significant decrease in cardiovascular risk brought about by lowering LDL cholesterol due to statin therapy. Additionally, the impact of statin therapy on glycemic control in individuals with diabetes was not dissimilar from that observed in cases of new-onset diabetes.

The results also suggested that the incidence rates of new-onset diabetes were significantly higher for the trials involving high-intensity statin regimens in both the intervention and placebo groups, as compared to trials evaluating moderate or low-intensity statin regimens. The researchers believe this significant difference in event rates could be because the trials evaluating the high-intensity regimens had a higher follow-up frequency, including more frequent blood glucose tests.

Conclusions

Overall, the findings suggested that while statin therapy was associated with an increase in the rate of new-onset diabetes diagnoses, the association was moderate and dose-dependent. Furthermore, the risk of new-onset diabetes was higher in individuals whose glycemic markers were already quite close to the threshold for diagnosing diabetes. Any potential increase in cardiovascular disease risk due to the hyperglycemic effect of statins was mitigated by the overall reduction in cardiovascular risk due to statin therapy.