The Adult Treatment Panel (ATP)-III guidelines list diabetes as a coronary heart disease (CHD) risk equivalent (1). Therefore, the LDL cholesterol goal of <100 mg/dl for patients with diabetes is equivalent to that of patients with known CHD (1,2). Hydroxymethylglutaryl-CoA reductase inhibitor (statin) therapy is recommended as first-line treatment in diabetic patients with elevated LDL cholesterol levels (2,3). Despite maximum statin doses, not all patients are able to reach this goal. In addition, some patients experience drug-induced side effects when statin doses are titrated upwards in an attempt to reach that goal. In such cases, lipid-lowering combination therapy may be warranted because doubling the statin dose has been shown to only incrementally improve LDL cholesterol reduction, whereas the use of lipid-lowering medications with different mechanisms of action have demonstrated synergistic effects (4).
Ezetimibe (Zetia; Merck/Schering-Plough Pharmaceuticals, North Wales, PA) is the first in a novel class of antihyperlipidemic agents called 2-azetidinones, which act as a selective cholesterol absorption inhibitor. Ezetimibe is indicated for the treatment of primary hypercholesterolemia, alone or in combination with statin therapy (5). Compared with placebo, ezetimibe as monotherapy decreases LDL cholesterol levels by 16–19% (6–8). When it is added to statin therapy, ezetimibe demonstrates a significant 15–20% additional mean percent reduction in LDL cholesterol levels compared with statin use alone (9–11). To date, the safety and efficacy of ezetimibe in a diabetic population has not been reported. The objective of this report was to retrospectively determine the effectiveness and safety of ezetimibe in patients with diabetes at a private endocrinology practice.
The study population consisted of patients with diabetes who were prescribed Zetia, had no medication changes between baseline and follow-up visits, had fasting values obtained at baseline and follow-up, and received ezetimibe for a minimum of 6 weeks. The 23 identified patients were elderly (63.2 ± 12.4 years of age), were obese (95.8 ± 24.9 kg), and had long-standing diabetes (16.3 ± 12.2 years), but had excellent control of glucose levels (HbA1c 6.9 ± 1.1%) and blood pressure (115.9 ± 9.3 and 69.1 ± 4.1 mmHg for systolic and diastolic, respectively). Of the 23 patients, 2 had type 1 diabetes. At baseline, 74% (17 of 23) of patients were receiving statin therapy (for a minimum of 6 months), including 3 patients who received combination therapy with micronized fenofibrate, gemfibrozil, and sustained-release niacin, respectively. Two additional patients were receiving sustained-release niacin and micronized fenofibrate monotherapy, respectively. The remaining four patients received no antilipidemic medication at baseline.
The average time of follow-up was 83 days. With the addition of ezetimibe, there was a statistically significant 21% mean reduction in total cholesterol (219.6 ± 44.5 to 174.3 ± 39.9 mg/dl; P < 0.001) and a 34% average decrease in LDL cholesterol levels (129.3 ± 36.2 to 85.9 ± 27.2 mg/dl, P < 0.001). There were no significant changes in triglycerides (P = 0.215), HDL cholesterol (P = 0.06), aspartate aminotransferase (P = 0.444), or alanine aminotransferase (P = 0.319) values. Seventy percent of patients (16 of 23) had an LDL cholesterol level <100 mg/dl.
Ezetimibe represents a safe and effective treatment for patients with diabetes who are not at their LDL cholesterol goals. Clinicians should consider ezetimibe as a reasonable addition to statin therapy for diabetic patients unable to tolerate statins at high doses or for patients who fail to reach therapeutic end points on maximum-dose statin therapy.
References
R.S.B. has received honoraria from Merck Pharmaceuticals.
