"Professional societies and expert groups should make clear recommendations about the need for routine vs. targeted glucose testing, as well as the frequency. Consensus guidelines don’t yet exist. The new statin label eliminates testing liver function. Will this be replaced by excessive testing of blood glucose, a practice that could be burdensome to patients and clinicians and drive up health care costs?" she said in an interview.
The dilemma physicians also face when deciding whether to prescribe a statin to patients toward the low end of the cardiovascular risk spectrum is that the same risk factors that might flag patients with a high risk for insulin resistance, hyperglycemia, and the development of type 2 diabetes – factors such as obesity, inadequate physical activity, elements of metabolic syndrome, and a "prediabetic" fasting plasma glucose level of 110-125 mg/dL – also function as cardiovascular disease risk factors.
"It would be a mistake to say that anyone at high risk for diabetes should be denied a statin because these people are also at high risk for cardiovascular disease," Dr. Manson said. She recommended that patients on statin treatment at least be told to be on the alert for developing new symptoms of diabetes: frequent thirst, frequent urination, and blurred vision. "And lifestyle modifications should be intensified to reduce both diabetes and CVD risk."
"The excess risk for diabetes is concentrated in the people with fasting blood sugars in the 115- to 125-mg/dL range" said Dr. Roger S. Blumenthal, professor of medicine and director of preventive medicine at Johns Hopkins Medical Institutions in Baltimore. "A lot of those people are clearly insulin resistant. We almost always have a fasting plasma glucose [when patients are about to start on a statin] as part of a basic lipid profile. With physicians aware of the association, I think this will focus more attention on vulnerable patients in the 115- to 125-mg/dL range, who are headed for diabetes if they don’t make significant improvements in their diet and exercise habits. It’s reasonable to look at glucose and tell patients that a statin might potentially raise their blood sugar by 5-7 mg/dL, but exercising and dropping some excess weight will significantly improve their blood sugar."
Dr. Prakash Deedwania
Targeted use of plasma glucose testing in statin recipients who seem to have the greatest risk for developing diabetes also received endorsement from Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, in Fresno. He suggested possibly doing annual testing of patients with metabolic syndrome, those who are obese, those with a family history of diabetes, and patients who have previously shown impaired glucose tolerance on a tolerance test.
If a patient’s fasting plasma glucose began to creep up on a statin regimen, "I’d look for other reasons, such as did they gain weight?" he said. Seeing a possible hyperglycemic effect should also prompt a reassessment of whether the patient benefited from the statin, and whether they have made necessary lifestyle changes like improved diet and increased exercise. Rising blood sugar could be used to help motivate a patient to do better on lifestyle measures, and trigger a reevaluation of whether the patient is, on balance, benefiting from the statin, he said. Changing the statin used or the dosage is tricky, because no evidence exists now to support such steps.
But because the biggest signal for the prodiabetic effect of statins came in results from the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) (N. Engl. J. Med. 2008;359:2195-207), the current perception among at least some physicians is that rosuvastatin (Crestor) poses the biggest hyperglycemic risk. "Some physicians might consider changing [the prescribed statin] from rosuvastatin to simvastatin or atorvastatin," Dr. Blumenthal said.
The FDA took the right step in adding the hyperglycemia information to statin labeling, said Dr. Deedwania. "They give the data, and leave it up to physicians to make their own conclusions."
Dr. Stephen J. Nicholls
As a consequence of the FDA’s actions "a lot more physicians will pay attention to glucose as they put patients on statins. The evidence is consistent, and most now agree that it’s real," said Dr. Stephen J. Nicholls, a cardiologist at the Cleveland Clinic. "But these are not completely healthy people with low glucose levels who suddenly, on a statin, become diabetic. What this reinforces is that while there will continue to be a lot of people who require statin treatment, the cornerstone of treatment is lifestyle change: diet, exercise, and weight loss. There is a continuum of risk: Patients at higher risk will benefit from a statin; for patients at very low risk use lifestyle. And if you put a patient on a statin, you need to keep an eye on them."
Dr. Robinson, Dr. Manson, and Dr. Blumenthal said that they had no relevant financial disclosures. Dr. Deedwania said that he has been a consultant to Pfizer, Amarin, and Amgen. Dr. Nicholls said he has received research support from AstraZeneca and has been a consultant to AstraZeneca, Merck, and Pfizer.