Statins Up Type 2 Diabetes Risk, Overweight at Greatest Risk

Miriam E. Tucker

March 13, 2019

Further evidence that statin use increases the risk for the development of type 2 diabetes has been published, with the work showing that the risk is particularly high in people who are overweight, obese, or have prediabetes.

Findings from the prospective, population-based study were published online March 5 in the British Journal of Clinical Pharmacology by Fariba Ahmadizar, PhD, of the department of epidemiology at Erasmus University Medical Centre, Rotterdam, the Netherlands, and colleagues. 

Several previous observational studies and trials have reported an increased risk of incident type 2 diabetes in people treated with statins, but most of them have been lacking in details about glycemic traits.

The incidence seen in observational studies such as the current one has been much higher than in randomized trials, 44% versus 9% to 13%, Ahmadizar and colleagues note.

In their study of 9535 adults older than 45 years without diabetes at baseline, during follow-up those using statins developed higher concentrations of serum fasting insulin, higher rates of insulin resistance, and were 38% more likely to develop type 2 diabetes. The risk was more significant among those who were overweight or obese.

"This suggests that it is necessary to take statin diabetogenicity into consideration in clinical practice [with] rigorous preventive strategies such as glucose control and weight reduction in patients when initiating statin therapy, which might help in minimizing the risk of diabetes," the authors say.

Asked to comment, cardiologist Robert H. Eckel, MD, professor of medicine and director of the Lipid Clinic at the University of Colorado Hospital, Aurora, stressed to Medscape Medical News, "It’s important to remember that even if statin-treated patients develop type 2 diabetes, the cardiovascular benefit remains."

Eckel advised that clinicians follow the 2018 American College of Cardiology/American Heart Association cholesterol guidelines.

But he also said that because the risk seen in the current study was somewhat higher than that seen in prior observational studies, "I would recommend that HbA1c in the 6.2% to 6.4% range be monitored more closely in statin-treated patients."

Statin Use, Higher Glycemia Linked

In this longitudinal follow-up study of 9535 people without diabetes at baseline, which took place in 1997-2012, the median follow-up period was 4 years. Participants were a mean age of 64 years at baseline, 58% were women, and 64.5% were overweight or obese.

A total of 968 (10%) participants had taken statins, including simvastatin (57%), atorvastatin (25.5%), and pravastatin (10.3%). Over the study period, 7.5% (716) of participants developed type 2 diabetes. 

In an initial cross-sectional analysis adjusted for age, gender, cohort (by time period), smoking status, alcohol consumption, physical activity, education, body mass index (BMI), and hypertension, baseline statin use was significantly associated with both increased serum fasting insulin concentrations and HOMA-IR (Homeostatic Model Assessment for Insulin Resistance).

However, serum fasting glucose levels lost significance following the adjustments for BMI and hypertension.

Because of that, Ahmadizar and colleagues say, "our finding suggests that the association between statins and diabetes could be through insulin secretion/resistance."

There was no effect of statin type or dose. In a longitudinal follow-up analysis, ever-use of statins was significantly associated with development of type 2 diabetes, with hazard ratios (HR) of 1.64 before and 1.38 after the adjustments, both of which were significant.

The risk was significant among current but not past statin users, with hazard ratios of 1.52 and 1.18, respectively. 

Again, no significant effect of statin type or dose on incident type 2 diabetes risk was seen in this analysis, although longer duration of statin use did raise the risk.

Link Between Statins/Diabetes Only Significant in Men, Higher BMIs?

In further sensitivity analyses stratified for BMI at baseline, the association between statins and type 2 diabetes was only significant among those who were overweight or obese but not among those with normal BMI (HR, 1.42 vs 1.18).

And when stratified by gender at baseline, the finding was significant only in men and not women (HR, 1.52 vs 1.28).

Eckel commented: "It was disappointing to have no HbA1c data, but in general those with higher HbA1c without type 2 diabetes are at higher risk, which is supported by their glucose data."

He also faulted the lack of data on family history of type 2 diabetes and questioned the findings on men and the lack of significance for statin dose, noting "statin dose may still be important despite what they found."

Eckel is a member of advisory boards and/or is a consultant for Sanofi, Regeneron, Kowa, Novo Nordisk, Merck, and Endece.

Br J Clin Pharmacol. Published online March 5, 2019. Abstract

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