More Data on Diabetes Risk With Statins

From Heartwire

Sue Hughes

March 31, 2011 (San Francisco) —
A new analysis of three major trials with atorvastatin (Lipitor, Pfizer) has suggested that the risk of new-onset diabetes with statins appears to be dose dependent and related to the strength of cholesterol lowering achieved with the statin--ie, the more powerful the statin, the higher the risk of diabetes.

But the authors, as well as other experts, stress that the benefits of statin treatment still clearly outweigh the risks in patients with coronary or cerebrovascular disease.

This latest analysis, published in the April 5, 2011 issue of the Journal of the American College of Cardiology, was conducted by a team led by Dr David Waters (San Francisco General Hospital, CA).

He explained to heartwire that last year's meta-analysis of statin studies showed a small increase (HR 1.09) in new-onset diabetes in patients taking statins vs those on placebo. But other clinical predictors were not examined, and only one of the 13 trials in this analysis involved atorvastatin, compared with six with pravastatin and three with rosuvastatin (Crestor, AstraZeneca).

Waters et al wanted to look at the risk of diabetes specifically with atorvastatin, and they did this with data from three large studies–-TNT (comparing 80 mg and 10 mg/day of atorvastatin in patients with stable coronary disease), IDEAL (atorvastatin 80 mg vs simvastatin 20 mg/day in post-MI patients) and SPARCL (atorvastatin 80 mg/day vs placebo in patients with a recent stroke or transient ischemic attack).

Results showed that atorvastatin 80 mg was associated with an increased risk of new-onset diabetes compared with placebo in the SPARCL study, and in the other two trials atorvastatin 80 mg was associated with a trend toward more diabetes than lower doses of either atorvastatin or simvastatin.

Frequency of New Onset Diabetes (%) in SPARCL, TNT, and IDEAL
Trial Atorvastatin 80 mg Control HR (95% CI) P
SPARCL 8.71 6.06 1.37 (1.08–1.75) 0.011
TNT 9.24 8.11 1.10 (0.94–1.29) 0.226
IDEAL 6.40 5.59 1.19 (0.98–1.43) 0.072

Waters commented: "We verified what was seen in the Lancet meta-analysis. We found a small increase in risk of developing diabetes with atorvastatin vs placebo, and a trend toward a greater effect with higher doses or more powerful statins."

But he noted that they could also predict which patients would develop diabetes from traditional risk factors--fasting blood sugar, body-mass index, hypertension, and elevated triglycerides.
"If patients had all four of these risk factors, they had a 25% risk of developing diabetes. If they had none of these risks factors, their risk was just 2%. That is not surprising, as we know these factors predict new onset diabetes."

"Not a Big Deal"

Waters told heartwire : "The biggest point I want to emphasize about this study is that patients should not stop taking statins because they are afraid of developing diabetes. I do not think this is a big deal.
If they have a history of heart disease or stroke, statins will reduce their risk of a new event by a huge amount. Compared with their risk of a cardiovascular event, their risk of developing diabetes is paltry."

He continued: "I would advise patents to keep taking their statins and do other things to lower their risk of diabetes--lose weight, control blood pressure, and exercise.
The risk of diabetes with these drugs is quite low--lower than with beta blockers, diuretics, niacin, and steroids."

In the paper, Waters et al note that the authors of the recent meta-analysis calculated that treating 255 patients with a statin for four years would induce one case of new-onset diabetes but would prevent 5.4 coronary deaths or MIs for each mmol/L reduction in LDL cholesterol.
"This benefit would be greater if strokes and coronary revascularizations were included. The benefits of statin treatment thus far outweigh the risks, particularly because it is uncertain as to whether new-onset diabetes itself increases risk," they write.

"This Will Not Alter My Use of Statins"

Commenting on the study for heartwire , Dr Roger Blumenthal (Johns Hopkins Medical Institute, Baltimore, MD) was not overly concerned about these latest results.
"The important point to emphasize is that the event rate in persons with new-onset diabetes on atorvastatin was considerably less than those patients who had diabetes at the start of the trial and was essentially no different from those who did not develop diabetes during the trial.
Similarly, those subjects in ALLHAT who developed diabetes on a thiazide did not experience a higher CVD event rate," he said. "I emphasize to patients that the benefits of statins far outweigh their risks. If patients do a better job at increasing their exercise and improving their exercise habits, their glucose levels likely will improve. This will not alter my use of statins," Blumenthal added.

Metabolic-Syndrome Patients Need Aggressive Statin Treatment

Dr William Boden (University at Buffalo Schools of Medicine and Public Health) also said he would not read too much into this study. "At most, there is an association--not causality--of high-dose atorvastatin and new-incident type 2 diabetes. To me, what really comes across is that the substrate for developing new-onset diabetes is the existence of metabolic syndrome."

Boden further pointed out that the NCEP ATP III guidelines advocate aggressive treatment with statins in patients with metabolic syndrome. "We usually seek to achieve the optional, more aggressive LDL target of <70 mg/dL in these patients. Thus, one would expect that more patients with metabolic syndrome would be treated with high-dose atorvastatin to achieve this more stringent LDL target. So, then, it shouldn't be surprising that there is an association between high-dose atorvastatin and the development of diabetes in these patients--because they are at much higher risk for developing diabetes in the first place."

He added: "All this means to me is that one needs to be vigilant for observing whether patients with metabolic syndrome go on to develop type 2 diabetes. Given the robust findings across multiple primary- and secondary-prevention trials of statins showing that these agents decrease death, MI, stroke, and vascular disease, I would strongly argue the net clinical benefit of statins in such patients far, far outweighs the <10% risk of developing diabetes, and such patients are even more compelling candidates for aggressive risk-factor control and intervention with aggressive statin therapy."