An article published Online First and in an upcoming edition of The Lancet reports that new research based on a meta-analysis of thirteen statin trials has shown that use of statins increases the risk of developing type 2 diabetes by 9 percent. Still, the absolute risk is low, especially when compared with the beneficial effect that statins have on reducing coronary events. The article is the work of Professor Naveed Satar and Dr David Preiss, Glasgow Cardiovascular Research Centre, University of Glasgow, UK, and colleagues.

Trials of statin therapy on the risk of development of diabetes in patients given statins have had inconsistent findings. To eliminate this doubt, the authors did a meta-analysis of published and unpublished data in order to find out whether any relation exists between statin use and development of diabetes.

Thirteen trials from the period 1994 to 2009 were included. 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 haemodialysis, were excluded. The thirteen statin trials identified contained a total of 91,140 participants. Of these, 4,278 developed diabetes over an average of four years. A total of 2,226 were assigned statins and 2,052 were assigned control therapy. Statin therapy was associated with a 9 percent increased risk for developing diabetes. There was general consistency in risk across the different trials. Additional analysis showed that the risk of development of diabetes with statins was higher in trials with older participants. On the other hand, baseline body-mass index and change in LDL (bad) cholesterol concentrations did not 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 researchers highlight that the findings do not prove that statin therapy raises diabetes risk via a direct molecular mechanism. However, the possibility should be considered. On the other hand, the increased risk could be in some way linked to statin therapy. A slight improvement of survival on statins does not compensate for the increased risk of developing diabetes. Although the authors find it doubtful, they say the increased diabetes risk in those given statins could be a chance finding.

In perspective, treatment of 255 patients with statins for four years would result in one extra case of diabetes. However, for 1 mmol/L reduction in LDL (bad) cholesterol concentrations that statins would cause, the same 255 patients could expect to experience five less major coronary events such as coronary heart disease death or non-fatal heart attack.

The authors advise that monitoring older people receiving statin therapy for development of diabetes could be beneficial since they seem to be more at risk. They explain: “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 write in conclusion: “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. 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 associated note, Dr Christopher P Cannon, Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston; and TIMI Study Office, Boston, MA, USA, comments on the study. He discusses how the authors of this study projected that 5•4 deaths or heart attacks would be avoided over those four years. Also, nearly the same number of strokes or coronary revascularisation procedures would also be avoided. Dr Cannon remarks: “Thus the benefit [of taking statins] in preventing total vascular events to the risk of diabetes is a ratio of about 9:1 in favour of the cardiovascular benefit. Thus the benefit seems to greatly outweigh the risk.”

He say in closing: “Nonetheless, 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. Thus, whilst a new risk of statins has been identified, the risk seems small and far outweighed by the benefits of this life-saving class of drugs.”

“Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials”
Naveed Sattar, David Preiss, Heather M Murray, Paul Welsh, Brendan M Buckley, Anton J M de Craen, Sreenivasa Rao Kondapally Seshasai,
John J McMurray, Dilys J Freeman, J Wouter Jukema, Peter W Macfarlane, Chris J Packard, David J Stott, Rudi G Westendorp, James Shepherd,
Barry R Davis, Sara L Pressel, Roberto Marchioli, Rosa Maria Marfisi, Aldo P Maggioni, Luigi Tavazzi, Gianni Tognoni, John Kjekshus, Terje R Pedersen,
Thomas J Cook, Antonio M Gotto, Michael B Clearfield, John R Downs, Haruo Nakamura, Yasuo Ohashi, Kyoichi Mizuno, Kausik K Ray, Ian Ford
DOI: 10.1016/S0140-6736(09)61965-6
The Lancet

Stephanie Brunner (B.A.)