Over the past few years, emerging evidence has led to concerns that statin use may increase the risk of type 2 diabetes (T2D). The US Food and Drug Administration responded with a requirement in 2012 that labels state that statins may raise glycated hemoglobin (HbA1C) and fasting glucose levels.1 Despite reassurance that the benefits far outweigh any potential risk of T2D offered by the Statin Diabetes Safety Task Force,2 a nagging worry has lingered among consumers and remained an unresolved concern for clinicians.
The diabetogenic impact of statin treatment, in general, is relatively modest, said study author, Joshua Knowles, MD, PhD, assistant professor of cardiovascular medicine at Stanford University. The findings revealed metabolic markers--insulin resistance combined with either an elevated triglyceride (TG >1.7 mmol/l) or body mass index (BMI ≥27.0 kg/m2)-- to clinicians for use in predicting which patients may be at highest risk of developing T2D if given a statin.3
"If you are prediabetic and have high triglycerides, the risk of getting diabetes was 17% without a statin, and if you added a statin on top of that, your risk was about 23%,"3 said Dr. Knowles, summarizing the study findings as published in the American Journal of Cardiology.
On the other hand, Dr. Knowles said, ''if you don’t have prediabetes and are not overweight and don't have high triglycerides, the risk [of getting diabetes] is very, very low. Adding a statin doesn't seem to change a patient’s risk that much." The rate of developing diabetes in individuals on a statin was about 3%, which was essentially identical to the same group who were not on the medications.3
These findings build on previous research, said Seth Baum, MD, president of the American Society for Preventive Cardiology who comments to Endocrine Web. It will also help physicians put the risk of developing diabetes in perspective—a worry that most patients talk about, according to Dr. Baum.
"This will help clinicians fine tune, which patients might be more susceptible to developing incident diabetes during treatment with statin therapy," Dr. Baum told EndocrineWeb, a preventive cardiologist and clinical lipidologist in Boca Raton. "If a person is at higher risk to develop prediabetes, perhaps this will lead to a more impactful discussion with the patient, resulting in better control of the diabetes risk factors."
The physician can explain with clearer certainty to patients that "the more risk factors you have, the more likely you will be to convert to becoming a diabetic," Dr. Baum said. That information may motivate patients to make lifestyle changes to reduce their weight, their blood glucose, and their triglycerides.
"This paper was not meant to discourage statin use," said Dr. Knowles, whose Stanford University team worked with researchers from Kaiser Permanente and the University of California at San Francisco.3 "The real message is, statins are needed in this population, and we really need to concentrate hard on exercise and weight loss in the prediabetes and high triglyceride population'' who are most at risk for developing T2D.
The study findings suggests that the risk of developing diabetes while on statin therapy disproportionately affects those who already have a predisposition for diabetes or high triglycerides. "We really need to target efforts [for lifestyle modification] in that population," Dr. Knowles said.
''What our paper shows is, without a statin your risk of diabetes goes up over time," said Dr. Knowles, if you have prediabetes, high triglycerides, elevated HbA1C, or a high BMI. Then, "if you add a statin, those risks magnify, especially in the highest risk categories," he said.
Individuals taking a statin who have the greatest insulin resistance are believed to be at the highest risk given that insulin resistance is an independent predictor of type 2 diabetes.
Researchers followed more than 22,00 patients for nearly 5 years, looking at insulin resistance, and evaluating whether a diagnosis of prediabetes combined with either elevated triglycerides (TG more than 1.7 mmol/l) or high body mass index (BMI equal to or greater than 27) could help predict T2D among those who began taking a statin to reduce their risk of cardiovascular disease.3
The patients were randomly assigned to statin therapy (10 or 80 mg/day of atorvastatin) or placebo. Dividing the 22,000 patients into four groups, the researchers computed actual prisks for each category after following the patient for a median of 4.9 years.
The four groups are described here:
Other groupings were also done, substituting BMI values, either below 27kg/m2 or 27 and above, for the triglyceride levels.
A diagnosis of diabetes was made after at least two fasting plasma glucose concentrations of 126 mg/dl or higher, an increase in FPG of 37 mg/dl or more, or a clinical diagnosis of diabetes.
Overall, 8.2 % of the total patient population developed diabetes during the follow-up period. However, the percent who developed diabetes ranged from a low of less than 3% to nearly 23%, depending on individual risk factors.
Dr. Knowles reports no financial conflicts. Coauthors are on the advisory board of Amgen and participate in clinical trial committees for Pfizer, Sanofi-Aventis and other pharmaceutical firms and receive consulting fees from Novo Nordisk and Pfizer.
1. US Food and Drug Administration. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs., 2012. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm. Accessed: November 18, 2016.
2. Maki KC, Ridker PM, Brown WV, Grundy SM, Sattar N5 for the Diabetes Subpanel of the National Lipid Association Expert Panel. An assessment by the Statin Diabetes Safety Task Force: 2014 update. J Clin Lipidol. 2014;8(3 Suppl):S17-29.
3. Kohli P, Knowles JW et. al. Metabolic Markers to Predict Incident Diabetes Mellitus in Statin-Treated Patients (from the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trials), Am J Cardiol. 2016;118(9):1275-1281.
4. Lillioja S, Mott DM, et. al. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. New Engl J Med. 1993:329: 1988-1992.