Statins and diabetes: Whether benefits outweigh the risks
Several recent publications have addressed the issue of whether statins increase the risk for new-onset diabetes, although statins have proven cardiovascular benefits and are generally well tolerated by most patients.
Results from the JUPITER trial showed that rosuvastatin increased the risk for new-onset diabetes by 27% as compared with placebo. Increased risks also have been shown with other statins such as atorvastatin and simvastatin. However, the WOSCOPS trial showed a reduction in the risk for new-onset diabetes of 30% with pravastatin.
In 2010, Sattar and colleagues conducted a meta-analysis of 13 trials involving more than 90,000 patients and found that the risk for new-onset diabetes increased by 9% after 4 years of statin therapy. This equated to one additional case of diabetes when 255 patients were treated with a statin for 4 years. The elderly appeared to be at greatest risk.
This year, Carter and colleagues conducted a population-based retrospective cohort study in Canada involving patients aged 66 years or older. They used prescription and diagnosis databases to obtain the data. Their results showed that compared with pravastatin, new-onset diabetes increased with the use of atorvastatin (HR=1.22; 95% CI, 1.15-1.29), rosuvastatin (HR=1.18; 95% CI, 1.10-1.26) and simvastatin (HR=1.10; 95% CI, 1.04-1.17). No increase was associated with the use of lovastatin (HR=0.99; 95% CI, 0.86-1.14) or fluvastatin (HR=0.95; 95% CI, 0.81-1.11). Absolute risks were as follows: simvastatin, 26 cases per 1,000 person-years; atorvastatin, 31 cases per 1,000 person-years; rosuvastatin, 34 cases per 1,000 person-years; and pravastatin, 23 cases per 1,000 person-years. A subgroup analysis adjusting for dose caused the risk with rosuvastatin to become nonsignificant, whereas results for the other statins remained consistent.
In a review article on this issue also published this year, Goldstein and colleagues found that no trials have been completed with risk for diabetes with statins as the primary endpoint. They then reviewed each trial that has collected this data and concluded that statins increase the risk for new-onset diabetes by 1 to 6 cases per 1,000 patients treated for 1 year. Diabetes risk appeared to be related to the intensity of therapy and potency of the statin (more potent agents had higher risk). It also appears that certain groups are at higher risk, including the elderly, females and Asians. An interesting question they raise, which remains unanswered, is whether long-term benefits of statins outweigh any increased risk for diabetes.
Although it is not known exactly how statins may increase the risk for diabetes, there are several possible mechanisms. These include impaired insulin secretion by disruption of calcium channels and/or mitochondrial function; decrease in adipocyte insulin-responsive glucose transporter (GLUT4) resulting in increased insulin resistance; and skeletal muscle wasting leading to insulin resistance.
Goldstein and colleagues offer several suggestions to minimize the risk for new-onset diabetes with the statins. These include not using high doses of statins in the elderly, females or Asians. Other suggestions revolve around prevention, such as following the Mediterranean diet, exercise and minimizing sugar.
Although there appears to be some, albeit relatively small, association between statin use and new-onset diabetes, the proven benefits of statins likely outweigh any risk, especially in those at moderate to high risk for diabetes.