Lancet: Increased diabetes risk with statins does not outweigh their benefits

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The use of statins increases the risk of developing type 2 diabetes by 9 percent; however, the absolute risk is low, especially when compared with the beneficial effect that statins have on reducing coronary events, according to a meta-analysis of 13 statin trials published online Feb. 16 in the Lancet.

Trials of statin therapy have had conflicting findings on the risk of developing diabetes. To resolve this uncertainty, the authors performed a meta-analysis of published and unpublished data to determine whether any relation exists between statin use and development of diabetes.

Naveed Satar, PhD, and David Preiss, MD, from Glasgow Cardiovascular Research Centre, University of Glasgow, Scotland, and colleagues included 13 trials from the period 1994-2009, and each trial had more than 1,000 patients, with identical follow-up in both the statin and non-statin groups and duration of more than one year. Trials of patients with organ transplants or who needed hemodialysis were excluded.

The 13 statin trials identified contained 91,140 participants, of whom 4,278 (2,226 assigned statins and 2,052 assigned control therapy) developed diabetes over an average of four years, according to the authors.

The researchers reported that statin therapy was associated with a 9 percent increased risk for developing diabetes, with broad consistency in risk across the different trials.

Also, further analysis indicated that the risk of developing diabetes with statins was higher in trials with older participants, However, the authors wrote that neither baseline body-mass index nor change in LDL cholesterol concentrations appear to influence the statin-associated risk of developing diabetes.

Treatment of 255 patients with statins for four years resulted in one extra case of diabetes, the authors reported.

Investigators stressed that the results do not prove that statin therapy raises diabetes risk via a direct molecular mechanism, though the possibility should be considered. Alternatively, the increased risk could be indirectly linked to statin therapy. Slightly better survival on statins is not able to explain the increased risk of developing diabetes. Although they believe it unlikely, the authors wrote that the increased diabetes risk in those given statins could be a chance finding.

For context, the researchers said that the 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 cholesterol concentrations (that statins would cause) the same 255 patients could expect to experience five less major coronary events.

The researchers recommended monitoring older people receiving statin therapy for the development of diabetes since they appear to be more at risk. “We recommend that development of diabetes is specified as a secondary endpoint in future large endpoint statin trials, and suggest that, when possible, reports of long-term follow-up in existing trials should also include incident diabetes," they wrote.

"In view of the overwhelming benefit of statins for reduction of cardiovascular events, the small absolute risk for development of diabetes is outweighed by cardiovascular benefit in the short and medium term in individuals for whom statin therapy is recommended,” Satar, Preiss and colleagues concluded. “We therefore suggest that clinical practice for statin therapy does not need to change for patients with moderate or high cardiovascular risk or existing cardiovascular disease. However, the potentially raised diabetes risk should be taken into account if statin therapy is considered for patients at low cardiovascular risk or patient groups in which cardiovascular benefit has not been proven.”

In an accompanying commentary, Christopher P. Cannon, MD, from the cardiovascular division at Brigham and Women's Hospital and Harvard Medical School in Boston, discussed how the study authors estimated that 5.4 deaths or heart attacks would be avoided over those four years, and nearly the same number of strokes or coronary revascularization procedures would also be avoided.

“Thus 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 cardiovascular benefit. Thus the benefit seems to greatly outweigh the risk," Cannon wrote.

"Nonetheless, this newly identified risk does warrant monitoring, and as such, in addition to periodic monitoring of liver-function tests and creatine kinase,