2007•Pharmacoepidemiology and Drug SafetyRequires access

High incidence of reduced plasma HDL cholesterol in diabetic patients treated with rosiglitazone and fibrate

Shlomo Keidar, Hadassa Guttmann, Tamar Stam, Ilana Fishman, Chen Shapira

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Abstract

BACKGROUND: A paradoxical plasma HDL-Cholesterol (HDL-C) reducing effect following combined fibrate and thiazolidinediones (TZDs) therapy was recently reported in occasional cases. As HDL-C level is inversely related to cardiovascular disease (CVD) risk, we have studied the incidence of reduced HDL-C level following mono- and combined therapy with these drugs in a large diabetic population. METHODS: This study was designed as a retrospective 5-year study. Lipid profile records of 54 000 diabetic patients were searched for transient reduction of HDL-C to levels lower than 17 mg/dL, which was correlated with fibrates and/or TZD treatment. RESULTS: Transient reduction in plasma HDL-C to values lower than 17 mg/dL was observed in 0.02% (2/11 175) of the patients treated with fibrates alone, none of the rosiglitazone-treated patients (0/3213) and in 1.39% (9/649) of patients treated with combination of fibrate and TZD. HDL-C lowering effect was reversible upon stopping either fibrate or rosiglitazone and in some patients it occurred within 2 weeks. In two of the patients, the effect was dose-dependent. CONCLUSION: Severe reduction in plasma HDL-C is not rare when TZD and fibrates are co-administrated to diabetic hyperlipidemic patients. As low plasma HDL cholesterol is a risk factor for CVD, the physician should be alert to this phenomenon.

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BACKGROUND: A paradoxical plasma HDL-Cholesterol (HDL-C) reducing effect following combined fibrate and thiazolidinediones (TZDs) therapy was recently reported in occasional cases. As HDL-C level is inversely related to cardiovascular disease (CVD) risk, we have studied the incidence of reduced HDL-C level following mono- and combined therapy with these drugs in a large diabetic population. METHODS: This study was designed as a retrospective 5-year study. Lipid profile records of 54 000 diabetic patients were searched for transient reduction of HDL-C to levels lower than 17 mg/dL, which was correlated with fibrates and/or TZD treatment. RESULTS: Transient reduction in plasma HDL-C to values lower than 17 mg/dL was observed in 0.02% (2/11 175) of the patients treated with fibrates alone, none of the rosiglitazone-treated patients (0/3213) and in 1.39% (9/649) of patients treated with combination of fibrate and TZD. HDL-C lowering effect was reversible upon stopping either fibrate or rosiglitazone and in some patients it occurred within 2 weeks. In two of the patients, the effect was dose-dependent. CONCLUSION: Severe reduction in plasma HDL-C is not rare when TZD and fibrates are co-administrated to diabetic hyperlipidemic patients. As low plasma HDL cholesterol is a risk factor for CVD, the physician should be alert to this phenomenon.

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Available abstract

BACKGROUND: A paradoxical plasma HDL-Cholesterol (HDL-C) reducing effect following combined fibrate and thiazolidinediones (TZDs) therapy was recently reported in occasional cases. As HDL-C level is inversely related to cardiovascular disease (CVD) risk, we have studied the incidence of reduced HDL-C level following mono- and combined therapy with these drugs in a large diabetic population. METHODS: This study was designed as a retrospective 5-year study. Lipid profile records of 54 000 diabetic patients were searched for transient reduction of HDL-C to levels lower than 17 mg/dL, which was correlated with fibrates and/or TZD treatment. RESULTS: Transient reduction in plasma HDL-C to values lower than 17 mg/dL was observed in 0.02% (2/11 175) of the patients treated with fibrates alone, none of the rosiglitazone-treated patients (0/3213) and in 1.39% (9/649) of patients treated with combination of fibrate and TZD. HDL-C lowering effect was reversible upon stopping either fibrate or rosiglitazone and in some patients it occurred within 2 weeks. In two of the patients, the effect was dose-dependent. CONCLUSION: Severe reduction in plasma HDL-C is not rare when TZD and fibrates are co-administrated to diabetic hyperlipidemic patients. As low plasma HDL cholesterol is a risk factor for CVD, the physician should be alert to this phenomenon.

Key concepts: Fibrate, Medicine, Rosiglitazone, Internal medicine, Incidence (geometry), Endocrinology, Cholesterol, Diabetes mellitus

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