Studies linking statins to diabetes receive media attention but should not distract clinicians from the goal of reducing cardiovascular risk.
Almost eight years after the Food and Drug Administration (FDA) added a warning to statin labels about the drugs increasing fasting blood sugar and hemoglobin A1C levels — and by inference raising the risk of new-onset diabetes — a new observational study on the diabetes risk received a great deal of media attention in 2019.
The study was picked up by Prevention magazine and National Public Radio’s People’s Pharmacy and led to eye-catching headlines: “Statins may double the risk of diabetes,” proclaimed medicalnewstoday.com. But the findings did not differ much from those of previous studies and should not affect statin use, experts tell Endocrine News.
Meanwhile, in a much lower-profile development, the American Heart Association released a scientific statement on statin safety concluding that the benefits of reducing cardiovascular risk far outweigh the risks from new-onset diabetes.
Although the relative risk of diabetes may sound large, the absolute risk is actually small. One of the randomized controlled trials that led to the FDA warning was the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial, which found a 27% increased risk of diabetes, but that diabetes occurred in 0.6% more participants randomized to receive rosuvastatin than placebo over two years.
“You need to treat a lot of people with statins for one person to get diabetes,” according to Savitha Subramanian, MD, associate professor of medicine in the Division of Metabolism, Endocrinology, and Nutrition at the University of Washington in Seattle. “Based on some of the data in the literature, if you treat a 1,000 people with statins, one person may get diabetes in one year.”
That New Study
The new study, published in Diabetes Metabolism Research and Reviews, was a retrospective cohort study of individuals enrolled in an insurance plan in the Midwest. It looked at the development of new-onset diabetes in patients who began taking statins compared with a matched control group who did not. It found that statins doubled the risk of developing diabetes, with the risk greatest among those taking statins for two years or longer. It found no differences by statin class or dose.
“If somebody needs a statin, it is always a discussion with the patient. You’ve got to talk with patients because there is so much out there, especially on the internet. People have a lot of opinions, and unfortunately, statins have come under so much flak, even though they are so beneficial.” – Savitha Subramanian, MD, associate professor of medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle
The study’s lead author, Victoria Zigmont, PhD, MPH, assistant professor at Southern Connecticut State University in New Haven, said that these and other findings from observational studies complement data from randomized controlled trials because they provide a window into how the drugs are being used in the real-world and their effects.
Effect on Patient Perception
The study’s significance may lie less in its new data and more in the media coverage it received — reports of a “doubled risk” could lead patients to be leerier of starting a statin.
“If somebody needs a statin, it is always a discussion with the patient,” says Subramanian.
“You’ve got to talk with patients because there is so much out there, especially on the internet. People have a lot of opinions, and unfortunately, statins have come under so much flak, even though they are so beneficial.”
The American Heart Association scientific statement provides an evidence-based foundation for counseling patients, says Connie B. Newman, MD, adjunct professor of medicine in the Division of Endocrinology, Diabetes, and Metabolism at the New York University School of Medicine in New York City. Newman chaired the expert panel that wrote the statement.
“Whenever you prescribe a statin to a patient, you should talk to them about lifestyle changes. Statins are adjunct to diet in the labels. They are not meant to be prescribed without a discussion about the importance of a healthy lifestyle.” – Connie B. Newman, MD, adjunct professor of medicine, Division of Endocrinology, Diabetes, and Metabolism, New York University School of Medicine, New York, N.Y.
Cardiovascular diseases remain the leading cause of death in the U.S. and globally, and statins have made a significant difference. The statement notes that “the most effective statins produce a mean reduction in low-density lipoprotein cholesterol of 55% to 60%” and have had “a major impact in reducing the incidence of cardiovascular diseases…including myocardial infarction and stroke, as well as death from cardiovascular diseases.”
Yet the statement notes that “studies … have reported an increase in patients stopping statins after negative media coverage and in major vascular events after stopping statin treatment.”
It notes that the risk of patients on statins developing diabetes “is largely confined to patients with multiple preexisting risk factors for diabetes mellitus. The absolute risk of statin-induced diabetes mellitus in major trials has been ≈0.2% per year. The size of any effect in routine clinical practice will depend on the baseline risk for developing diabetes mellitus in the patient population. In addition, in patients with diabetes mellitus, the average increase in HbA1c with initiation of statin therapy is small and thus is usually of limited clinical significance.”
It concludes: “Statin therapy substantially reduces cardiovascular events in those with and without diabetes mellitus and in the latter case, several cardiovascular events are prevented for every new diagnosis of diabetes mellitus. Furthermore, when considering the increase in newly diagnosed diabetes mellitus, it is important to note that this represents a far less dramatic and threatening event than the occurrence of myocardial infarction, stroke, or cardiovascular death.”
Any link between statins and diabetes should not lessen the appropriate use of statins, but only reinforces the need for patients to improve their lifestyles, which benefits both cardiovascular disease and diabetes risks, Newman notes. Losing weight, improving diet, and exercising more are all steps patients should be taking, and perhaps the greater risk of diabetes could give greater urgency to intensifying lifestyle therapies. “Whenever you prescribe a statin to a patient, you should talk to them about lifestyle changes,” Newman says. “Statins are adjunct to diet in the labels. They are not meant to be prescribed without a discussion about the importance of a healthy lifestyle.”
“There is quite a bit of research that shows that when physicians engage with their patients around enrollment in programs like the Diabetes Prevention Program, and the physicians follow up with them, then patients are more successful,” Zigmont says. “If physicians are comfortable having those conversations, there is research to show that this can be very beneficial for the patients in the long run.”
With one in four Americans over the age of 40 taking a statin and an increasing number of patients developing diabetes, these conversations — and the need for healthier lifestyles — are only growing in importance.
— Seaborg is a freelance writer based in Charlottesville, Va. He wrote about appropriate vitamin D levels in the January issue.