People taking statins have a small but apparently real increased risk of developing diabetes, according to a large new meta-analysis appearing in the Lancet. Sattar and colleagues used data from 13 controlled statin trials with over 91,000 subjects and found a 9% increase in the risk of diabetes over 4 years. The risk of developing diabetes with statins was highest in older patients, and was not found in patients 60 years old or younger.

In an accompanying comment, Chris Cannon acknowledged that “the finding does appear to be a class effect of statins,” but then took great pains to place the finding in context by balancing “this risk… and how it stacks up against the benefit.” Cannon noted that over four years one additional person will develop diabetes for every 255 patients who have been treated. By contrast, over the same 4 years 5.4 deaths or MIs will be avoided, as well as a similar number of strokes or revascularization procedures. “Therefore the benefit in preventing total vascular events to the risk of diabetes is a ratio of about 9:1 in favour of the cardiovascular benefit—the benefit seems to greatly outweigh the risk.”

Cannon writes that “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 who are on statins.”

Here is the Lancet press release:

STATINS INCREASE RISK OF DIABETES, BUT ABSOLUTE RISK IS LOW—ESPECIALLY WHEN COMPARED WITH REDUCTION IN CORONARY EVENTS

New research based on a meta-analysis of 13 statin trials has shown that use of statins increases the risk of developing type 2 diabetes by 9%. However, the absolute risk is low, especially when compared with the beneficial effect that statins have on reducing coronary events. These are the conclusions of an Article published Online First and in an upcoming edition of The Lancet, written by Professor Naveed Satar and Dr David Preiss, Glasgow Cardiovascular Research Centre, University of Glasgow, UK, and colleagues.

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 To resolve this uncertainty, the authors did a meta-analysis of published and unpublished data to determine whether any relation exists between statin use and development of diabetes.

The researchers included 13 trials from the period 1994–2009, and each trial had more than 1000 patients, with identical follow-up in both the statin and non-statin groups and duration of more than 1 year. Trials of patients with organ transplants, or who needed haemodialysis, were excluded. The 13 statin trials identified contained a total of 91 140 participants, of whom 4278 (2226 assigned statins and 2052 assigned control therapy) developed diabetes over an average of 4 years. Statin therapy was associated with a 9% increased risk for developing diabetes, with broad consistency in risk across the different trials. Further analysis showed that the risk of development of diabetes with statins was higher in trials with older participants, However, neither baseline body-mass index nor change in LDL (bad) cholesterol concentrations appear to influence the statin-associated risk of developing diabetes. Treatment of 255 patients with statins for 4 years resulted in one extra case of diabetes.

The authors stress 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 say the increased diabetes risk in those given statins could be a chance finding.

To put the findings into context, treatment of 255  patients with statins for 4 years would give one extra case of diabetes—but, for1 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 (ie coronary heart disease death or non-fatal heart attack).

The authors says that it could be useful to monitor older people receiving statin therapy for development of diabetes since they appear to be more at risk. They add: “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 conclude: “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 accompanying Comment, Dr Christopher P Cannon, Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston; and TIMI Study Office, Boston, MA, USA, discusses how the authors of this study estimated that 5·4 deaths or heart attacks would be avoided over those 4 years, and nearly the same number of strokes or coronary revascularisation procedures would also be avoided. Dr Cannon says: “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 concludes: “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.”