Evidence tilts toward diabetes risk with potent statins

Older patients treated with a high potency statin faced a 10 percent to 22 percent increased risk of new onset diabetes, according to results published online May 23 in BMJ. The authors of an accompanying editorial emphasized that the overall benefits outweigh the risks, “provided the treatment is targeted properly.”

Studies evaluating the association between statin use and new onset diabetes have been at odds. The JUPITER study, for instance, found that rosuvastatin significantly reduced the incidence of cardiovascular events compared with placebo, but it also had an increased risk in new onset diabetes. Other analyses associated diabetes risk with dose.

Aleesa A. Carter, PharmD, from Toronto General Hospital, and colleagues conducted a population-based cohort study based on administrative data from resources in Ontario to study the risk of new onset diabetes and statin use in statin naïve patients. They identified 471,250 patients who were 66 years old or older with no history of diabetes who initiated statin treatment between 1997 and 2010. The statins included in the evaluation were atorvastatin (Lipitor, Pfizer), fluvastatin (Lescol, Novartis), lovastatin (Mevacor, Merck), rosuvastatin (Crestor, AstraZeneca), simvastatin (Zocor, Merck) or pravastatin (Pravachol, Bristol Myers Squibb).

The primary outcome was new onset diabetes. Carter et al used pravastatin as the reference comparison group because it has shown improved insulin sensitivity in some studies.

Statins were prescribed for primary prevention to 48.3 percent of the patients and as secondary prevention to 51.7 percent. More than half of the prescriptions used atorvastatin. The median age was 73 years and 54.1 percent of patients were women.

Adjusted analyses showed that patients treated with atorvastatin had an increased risk of new onset diabetes of 22 percent compared with pravastatin; for rosuvastatin, 18 percent; and simvastatin, 10 percent. The use of fluvastatin and lovastatin held no significantly increased risk. The risk was similar in patients treated for primary or secondary prevention. Findings in subgroup analyses were consistent with primary results.   

The associated risk with rosuvastatin might depend on dose and duration. “The increased risk with rosuvastatin significantly decreased after covariate adjustment and became non-significant once dose was taken into consideration,” Carter et al wrote. “This could possibly represent greater use of rosuvastatin in patients with lower cardiovascular risk.”

They acknowledged that their study didn’t include risk factors such as weight and family history, blood measures and that it could be biased by residual confounding.

In an accompanying editorial, Risto Huupponen, MD, and Jorma Viikari, MD, PhD, both of the University of Turku in Finland, wrote that the study also may be confounded by prescribing bias; patients perceived to have a high-risk profile may have been prescribed a more potent statin at a higher dose.

Carter et al recommended that physicians consider risk when prescribing statins while Huupponen and Viikari wrote that the overall benefits of statins outweigh the risk of developing diabetes. The two editorial writers encouraged physicians to also incorporate lifestyle changes such as diet into treatment plans.

“All drugs have beneficial and harmful effects, and the doctor must find a justified balance between them,” Huupponen and Viikari reasoned. “For statins, prevention of cardiovascular events and the association with incident diabetes seem to go hand in hand; the greater the potency and higher the dose, the larger the effect for both outcomes. The balance favors use of statins, provided the treatment is targeted properly.”