"Although it does appear that statins may increase the chance of diabetes in high-risk patients, this should not stop us from using these drugs, as this small risk is outweighed by the substantial reduction in cardiovascular events."…
That was the conclusion of Dr. Barton Duell (Oregon Health & Science University, Portland), who was the discussant of five new studies on this issue reported at last week’s American Heart Association 2012 Scientific Sessions.
Presenter of one of the studies, Dr. David Waters (San Francisco General Hospital, CA), agreed with this view. He pointed out that the risk of diabetes vs cardiovascular benefits of statins in patients with prediabetes had been referred to as a "double-edged sword." But noting that cardiovascular events were much more serious than an increased risk of diabetes, Waters commented: "One edge of the sword is an awful lot sharper than the other."
Summarizing the new results presented at the AHA session, Duell noted that all five studies showed increased incidence of diabetes in statin users; the absolute increase in risk is low and appears to be proportional to the pretreatment risk of diabetes and the statin dose; and diuretics, beta blockers, and antidepressants may synergistically increase the diabetes risk seen with statins.
Duell added the mechanism behind the diabetes risk is unclear. "This is likely to be multifactorial and perhaps varies from one population to another." He said it is important that people not be discouraged from using statins because of this risk. "These really are excellent drugs, but new strategies are needed to help reduce the risk of diabetes in statin users, such as increased use of bile-acid sequestrants, reduced use of niacin, and better glucose monitoring," he added.
In his presentation, Waters reported an analysis of diabetes risk vs cardiovascular event reduction in two large studies of high-dose vs low-/moderate-dose statins: TNT and IDEAL.
Combining these two trials gave a total of 15,056 patients (after those with diabetes were excluded), who were divided into two groups: those at low risk of new-onset diabetes (8,825 patients with zero to one risk factor), and those at high risk (6,231 patients with two to four risk factors).
Results showed no difference in the development of new-onset diabetes with high-dose vs low-/moderate-dose statin in the low-risk population, but a 24% increase with the high-dose statin in high-risk patients. However, cardiovascular events were significantly reduced with the high-dose statin in both risk groups.
Asked about "net clinical benefit," Waters said this was difficult to work out, as "new-onset diabetes really does not compare with cardiovascular events, which were defined ascardiovascular death, MI, or stroke."
He added: "New-onset diabetes may count as one stroke against, but dropping dead from a cardiovascular event could be 100 strokes against. If you had to choose between one of these events, you are going to choose the diabetes."
Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: A collaborative meta-analysis of randomised statin trials. Lancet 2010; 375:735-742. Abstract
Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: A meta-analysis. JAMA 2011; 305:2556-2564. Abstract