Statins Linked to Diabetes and Complications in Healthy Adults

Troy Brown, RN

May 22, 2015

Statin use for primary prevention of cardiovascular disease among healthy adults has been linked to an increased risk for diabetes, diabetes complications, and overweight/obesity in a new retrospective cohort study that tracked individuals in a database for an average of 6.5 years.

"Whereas the increased risk of diabetes with statins is well-known, the increased risk of diabetic complications has not been previously described," write the authors, led by Ishak Mansi, MD, from the department of medicine, Veterans Affairs (VA) North Texas Health System, Dallas.

They report their findings in the Journal of General Internal Medicine and note that these are among the first data to show a connection between statins and diabetes in a relatively healthy group of people.

"The risk of diabetes with statins has been known, but until now it was thought that this might be due to the fact that people who were prescribed statins had greater medical risks to begin with," said Dr Mansi in a VA statement.

But this current work cannot be used to determine this risk/benefit because of missing information relating to various cardiovascular parameters, he and his colleagues say. Hence further research — including randomized controlled studies for prolonged periods and larger-scale prospective studies — are needed to develop a more complete risk/benefit assessment of statin treatment for primary prevention, they stress.

Asked to comment, Alvin C Powers, MD, director, division of diabetes, endocrinology and metabolism, at Vanderbilt University School of Medicine, Nashville, Tennessee, said: "I think the risk/benefit ratio in people with diabetes and statins remains the same as it was before, and the recommendations per the American Diabetes Association still are relevant."

"[The study] confirmed [an] increased risk for diabetes, and in this case, there were more complications of diabetes in the group taking statins, but it's not clear if that is a result of the statins or just the patient population," he told Medscape Medical News.

However, the author of another recent study, which reported the largest risk yet seen for diabetes with statins, Markku Laakso, MD, from the University of Eastern Finland and Kuopio University, has urged caution when considering statin use in primary prevention.

"Statins are not meant to be a treatment for everybody. Especially in women, who are at a lower risk of getting cardiovascular disease, maybe we should be more careful when we start statin treatment?" he said in March, when his work was published.

Dose-Response Relationship Observed

Statin use has long been associated with increased incidence of diabetes, but doctors have always maintained that the benefits of statin use outweigh this risk, particularly in a secondary-prevention population, given the powerful effects of statins in reducing cardiovascular risk.

But data on the long-term effects of these associations in a primary-prevention population are very limited, say Dr Mansi and colleagues. And the relationship between statin use and diabetic complications has not been adequately studied in such individuals, they note.

They identified Tricare beneficiaries who were evaluated between October 1, 2003 and March 1, 2012 and divided individuals into a group of statin users and a group of nonusers; about 75% of the statin prescriptions were for simvastatin.

The researchers excluded those who had preexisting cardiovascular disease, diabetes, or any life-limiting chronic diseases at baseline and used 42 baseline characteristics to generate a propensity score to match statin users and nonusers.

Of a total of 25,970 healthy adults at baseline, the researchers' propensity score matched 3351 statin users and 3351 nonusers.

The overall proportion of patients who developed diabetes during the follow-up period was approximately 14%, which is similar to recent national trends, the researchers say.

After adjustment for confounding factors — including the fact those who used statins had more visits with healthcare providers than nonusers — those who took statins still had an 85% higher risk of developing new-onset diabetes (odds ratio [OR], 1.85) and more than double the risk of diabetes with complications (OR, 2.53), as well as in increase in overweight/obesity (OR, 1.12) compared with those who didn't take statins.

The results also show that high-intensity statin therapy was associated with the highest risk of diabetes, diabetic complications, and overweight/obesity (adjusted ORs 2.55, 3.68, and 1.58, respectively), thereby demonstrating a dose–response relationship.

First Study to Show Risk of Diabetic Complications

Statin use was associated with a "very high risk of diabetes complications," says Dr Mansi, adding, "This was never shown before."

"Our findings will need to be confirmed by other studies, as they may have significant implications," he and his colleagues note.

"Our results indicate that extrapolating information from carefully selected patients in short-term randomized controlled studies to decades of statin use for primary prevention might not be appropriate.

"Additionally, statin effects on overall comorbidity, not only cardiovascular morbidity, need to become part of the risk/benefit assessment," they add.

Besides driving further research, Dr Mansi says he hopes the results will help inform conversations between patients and providers about the risks and benefits of statins.

"I myself am a firm believer that these medications are very valuable for patients when there are clear and strict indications for them," he said. "But knowing the risks may motivate a patient to quit smoking, rather than swallow a tablet, or to lose weight and exercise. Ideally, it is better to make those lifestyle changes and avoid taking statins if possible."

The authors and Dr Powers have disclosed they have no relevant financial relationships.

J Gen Intern Med. Published online April 28, 2015. Abstract


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