Response to Letter Regarding Article, “Statins and Risk of New-Onset Diabetes Mellitus”
Authors: Ravi V. Shah, Allison B. Goldfine
Journal: Circulation (2013)

We thank Dr Koh for his important comments on this emerging field. 1 We fundamentally agree that it is essential to consider the cardiovascular and metabolic health of the patient for whom statin therapy may be prescribed.Indeed, our suggestion is for clinicians to administer statin therapy when indicated by guidelines outlined by major professional societies.There is ample clinical evidence in both primary and secondary prevention that appropriately prescribed statin therapy leads to a significant reduction in cardiovascular events, including in those patients at lower risk of cardiovascular events. 2 Mechanisms by which statins increase incident type 2 diabetes mellitus remain incompletely understood.In addition to those suggested by Dr Koh, which may affect insulin secretion or action, statininduced myalgia may lead to decreased exercise, and other off-target effects may also be involved.There is no heterogeneity for risk of new-onset diabetes mellitus across trials that administered different individual statin agents, 3 suggesting that this is a class effect.The strongest predictors of newonset diabetes mellitus include older age, higher baseline fasting glucose concentrations, and features of the metabolic syndrome.This is also true for statin users. 4,5Although the association between statin therapy and new-onset diabetes mellitus is dose dependent, 3 the long-term clinical implications of these findings remain less clear.Although patients on intensive statin therapy experience a 12% higher risk of incident type 2 diabetes mellitus, these patients experience a 16% reduction in the risk of cardiac events; on balance, given the differences in the frequency of these diseases, this represents 2 more cases of diabetes mellitus for 6.5 fewer cardiac events per 1000 patient-years of follow-up on intensive-(relative to moderate-) dose statin therapy.Although diabetes mellitus is a serious health issue, the clinical implications of incident diabetes mellitus cannot be equated with those of myocardial infarction, stroke, or death. 3hether statin-induced diabetes mellitus is attended by the same long-term risk of increased macrovascular and microvascular complications remains uncertain.In contrast to Dr Koh's hypothesis that new-onset diabetes mellitus may generate a relative increase in deaths, in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study, over a median follow-up of only 1.9 years, participants previously considered to have low cardiovascular risk had clinically important health improvements, with a hazard ratio reduced 54% for myocardial infarction, 48% for stroke, 46% for revascularization, and 20% for deaths resulting from any cause. 6Patients with diabetes mellitus realize a relative risk reduction for major cardiovascular events, similar in magnitude to that for patients without diabetes mellitus without an increase in noncardiac death. 2 Current epidemiological data from the Centers for Disease Control and Prevention show that the ageadjusted prevalence rates of blindness and end-stage renal disease have decreased among patients with diabetes mellitus in recent years in the setting of increased statin use, along with improved screening, early detection, and multifactorial interventions.Thus, clinicians should monitor glucose or glycohemoglobin in patients with risk factors for diabetes mellitus who take statins, but they should continue to prescribe statins when indicated as part of a multifactorial approach to managing cardiovascular risk.