Diabetes risk of statins increased, but absolute risk low, outweighed by CV benefit

Use of statins appears to increase the risk for developing type 2 diabetes by 9%, according to the results of a new meta-analysis. However, the absolute risk is low, especially when compared with the beneficial effect of statins on coronary event reduction.

Trials of statin therapy have had conflicting results on the risk for development of diabetes. Thus, Naveed Sattar, MD, PhD, and colleagues conducted a meta-analysis of published and unpublished data to determine whether any relationship exists between statin use and development of diabetes.

The meta-analysis included 13 statin trials conducted from 1994 to 2009, including JUPITER, ALLHAT and PROSPER, among others. The trials included data on use of statins such as simvastatin (Zocor, Merck), atorvastatin (Lipitor, Pfizer) and pravastatin (Pravachol, Bristol-Myers Squibb). Trials in the analysis each had more than 1,000 patients, with identical follow-up in the statin and nonstatin groups and duration of more than one year. The researchers excluded trials of patients with organ transplants or who needed hemodialysis.

The 13 statin trials identified included 19,140 participants, of whom 4,278 developed diabetes during a mean four years (2,226 assigned statins and 2,052 assigned control therapy).

New risk identified

Statin use was associated with a 9% increased risk for developing diabetes (OR=1.09; 95% CI, 1.02-1.17). The researchers noted broad consistency in risk across the different trials.

“Physicians with patients prescribed statins appropriately — medium to high risk for cardiovascular disease — should not alter therapy as benefits to prevent CVD vastly outweigh any risk of diabetes,” Sattar and David Preiss, MRCP, of the University of Glasgow, Scotland, told Endocrine Today. “That noted, the risk–benefit for those at very low risk for CVD may be less clear-cut.”

Further analysis revealed that the risk for development of diabetes associated with statin use was higher in trials of older participants.

“The results suggest that age may be important to this adverse effect of statins — older people have a higher risk for coronary heart disease and, if deemed at medium to high risk of CVD on the basis of risk factor charts or algorithms, they should absolutely receive statins because, once again, benefits strongly outweigh any risks,” Sattar said.

Neither baseline BMI nor change in LDL concentration appeared to influence the statin-associated risk for developing diabetes.

Results further revealed that treatment of 255 patients with statins for four years would result in one extra case of diabetes. But, for 1 mmol/L reduction in LDL concentration, the same 255 patients could expect to experience five fewer major coronary events, such as coronary heart disease death or nonfatal myocardial infarction.

Benefits outweigh any risk

In an accompanying editorial, Christopher P. Cannon, MD, of the cardiovascular division at Brigham and Women’s Hospital and Harvard Medical School, and TIMI Study Office, Boston, said “the benefit [of taking statins] in preventing total vascular events to the risk of diabetes is a ratio of about 9:1 in favor of the [CV] benefit.

“Nevertheless, this newly identified risk does warrant monitoring, and, as such, in addition to periodic monitoring of liver-function tests and creatine kinase, it seems reasonable to add glucose to the list of tests to monitor in older patients on statins,” Cannon wrote.

Moreover, the researchers added, “the potentially raised diabetes risk should be taken into account if statin therapy is considered for patients at low [CV] risk or patient groups in which [CV] benefit has not been proven.

However, Sattar noted that he and his colleagues are unsure of the mechanism for the increased risk.

“Is it a direct effect of statins on glucose pathways or an indirect effect via a subtle reduction in activity levels due to muscle symptoms?” he said. “The latter is very speculative, but we are looking at this in more detail.”

The researchers recommended that future large endpoint statin trials use development of diabetes as a secondary endpoint and reports of long-term follow-up of existing statin trials include incident diabetes. – by Katie Kalvaitis

Sattar N. Lancet. 2010;doi:10.1016/S0140-6736(09)61965-6.

Cannon CP. Lancet. 2010;doi:10.1016/S0140-6736(10)60234-6.

This analysis finds a small absolute increase in the risk of diabetes that is dwarfed by the potential reduction in myocardial infarction and stroke risk that is seen with statin therapy. Statin therapy also stabilizes vulnerable plaques and slows the progression of atherosclerosis. This finding of a slightly higher risk of diabetes will not change guidelines or clinical practice, but it is thought-provoking. Perhaps we should simply stress the need to further improve one's dietary and exercise habits more when we prescribe a statin. Alternatively, our patients may subconsciously tend to slack off in terms of lifestyle changes when they feel they are being protected by a statin.

- Roger S. Blumenthal, MD
Director, Johns Hopkins Ciccarone Center for the Prevention of Heart Disease