High-Dose Statins May Increase Diabetes Risk

Experts Say Most Heart Disease Patients Are Better Off Taking a Statin, Despite Increased Diabetes Risk

Medically Reviewed by Laura J. Martin, MD on June 21, 2011
From the WebMD Archives

June 21, 2011 -- The strongest doses of cholesterol-lowering statin medications prevent heart attacks and strokes in patients with cardiovascular disease, but they may also modestly increase the risk of developing type 2 diabetes, a new study shows.

The study, a re-analysis of five clinical trials representing nearly 33,000 patients, found that the risk of developing type 2 diabetes increased slightly in patients who were on the most aggressive statin regimens compared to those on less powerful statin doses.

For every 498 patients who took high-dose statins for one year, there was one extra case of diabetes.

At the same time, however, the medications prevented one cardiovascular event such as a heart attack or stroke for every 155 people who took them.

“We found that for every one extra case of diabetes associated with this intensive statin use, you’d prevent approximately three people from having a major cardiovascular event,” says study researcher David Preiss, MRCP, a clinical research fellow at the British Heart Foundation Glasgow Cardiovascular Research Center at the University of Glasgow, in Scotland.

“We’re certainly not saying that people shouldn’t be taking a high-dose statin,” Preiss says. “If you’re somebody who’s at high risk of an event, it’s definitely favorable for you, but what you should be doing is every once in a while getting checked for diabetes.”

The new paper, which is published in the Journal of the American Medical Association, echoes two previous studies that noted an increased risk of type 2 diabetes in patients taking statins compared to those on a placebo.

“The evidence is strong that high doses of statins do slightly increase the risk of diagnosis of diabetes,” says Steven Nissen, MD, a cardiologist who is chair of the department of cardiovascular medicine at Cleveland Clinic, in Ohio. “However, the evidence is equally strong that patients on high doses have a reduction in cardiovascular events.”

High-Dose Statins and Diabetes

For the study, researchers solicited unpublished data from five studies that compared high and moderate doses of statins in 32,752 patients with either stable cardiovascular disease or a recent history of chest pain or heart attack. None of the patients had diabetes at the start of the study.

High-dose statins were 80 mg daily doses of Zocor, which is sold generically as simvastatin, or Lipitor.

Moderate-dose regimens varied but included daily doses of 10 mg to 40 mg of simvastatin, Lipitor, or pravastatin, which is also sold as Pravachol.

After being followed for an average of nearly five years, 2,749 patients developed diabetes -- 1,449 in the high-dose group and 1,300 of those on the moderate dose.

Over that same time period, about 20%, or 6,684 study participants, suffered a major cardiovascular event -- 3,134 on the intensive-dose therapy and 3,550 who were taking moderate statin doses.

There was no difference in diabetes risk between types of statins; only dose seemed to matter.

Patients on the high-dose regimens saw their odds of diabetes rise about 12%, while their odds of having a cardiac event dropped by about 16%, compared to patients on more moderate statin doses.

“It’s a good study,” says Spyros Mezitis, MD, an endocrinologist at Lenox Hill Hospital in New York City, who was not involved in the research.

“There are more studies that need to be done to really home in on this,” he says. “But statins are being used very widely right now, so we need to know anything that happens with the statins.

“What a clinician like myself takes out of it is that for people who are on high-dose statins and haven’t been diagnosed with diabetes, we should be checking for diabetes,” he says.

Statins and Diabetes

Experts say they aren’t sure what the link may be between statins and diabetes.

Nissen points out that many of the lifestyle factors that lead to cardiovascular disease, like abdominal obesity and a sedentary lifestyle, also contribute to diabetes.

“Many of us think that all that’s happening here is that patients who likely are destined to develop diabetes may have that diagnosis made a little bit earlier if given statins,” he says.

Experts say, though, that they aren’t sure why statins may hasten that diagnosis.

One theory is that muscle soreness caused by statins may make people less likely to move around. Being sedentary, in turn, increases the risk of diabetes.

Studies in mice have shown that statins may interfere with the action of the hormone insulin in muscle cells.

Even with the increased risk of diabetes, most people with heart disease are still better off taking a statin, experts say.

What should change now, many say, is the conversation that doctors have with patients about these drugs and the doses at which they’re used.

“We’ve just kind of been putting people on it and perhaps not giving them the full information about the downside, even if the downside is not very big,” Preiss says.

WebMD Health News



Preiss, D. Journal of the American Medical Association, June 22, 2011.

David Preiss, MRCP, clinical research fellow, British Heart Foundation Glasgow Cardiovascular Research Center, University of Glasgow, Scotland.

Steven Nissen, MD, chairman, department of cardiovascular medicine, Cleveland Clinic, Ohio.

Spyros Mezitis, MD, Lenox Hill Hospital, New York.

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