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Rosiglitazone reduces HDL cholesterol levels


Avandia ( Rosiglitazone ) is a member of the thiazolidinedione family of oral hypoglycemic agents used to improve glycemic control by increasing insulin sensitivity in muscle and adipose tissue and inhibiting hepatic gluconeogenesis.

Clinical trials using Rosiglitazone as monotherapy detected increases in levels of total cholesterol, low-density lipoprotein cholesterol ( LDL-C ) and high-density lipoprotein cholesterol ( HDL-C ) and decreases in levels of free fatty acids.

Decreased HDL-C levels were not seen in over 1400 patients treated with Rosiglitazone in clinical trials.
It is noteworthy that fibrates generally have a beneficial effect on HDL-C and triglyceride levels but occasionally have been associated with decreases in HDL-C and apolipoprotein A-I concentrations.

From Jan. 1, 2000, to Dec. 31, 2004, Health Canada received 1 report of a decreased HDL-C level suspected of being associated with Rosiglitazone. A 61-year-old woman with type 2 diabetes, hyperlipidemia, diabetic retinopathy and nephropathy had been taking Fenofibrate, Metformin and Glyburide for more than 1 year, and Perindopril for 9 months, before starting Rosiglitazone therapy, 8 mg daily.
The serum HDL-C level at this time was 1.06 mmol/L. Approximately 3 months later the HDL-C level had decreased to 0.27 mmol/L, the triglyceride level had increased from 1.4 to 3.4 ( target level in high-risk patients < 1.5 ) mmol/L, and the total cholesterol:HDL-C ratio increased from 4 to 15.4 ( target level in high-risk patients < 4 ).
Following discontinuation of the Rosiglitazone therapy after 7 months of use, there was an increase in the HDL-C level to 0.8 mmol/L and a reduction in the total cholesterol:HDL-C ratio to 5.3. The abnormal lipid values resolved 2 months after stopping the Rosiglitazone therapy. The reporter did not state whether treatment with Fenofibrate was continued. Subsequently, the patient developed symptoms of angina and underwent angioplasty.

The medical literature describes 3 cases of profound decreases in HDL-C and apolipoprotein A-I concentrations during treatment with Rosiglitazone.
Triglyceride levels also increased during treatment. In all 3 cases, the HDL-C level increased after withdrawal of the Rosiglitazone. Two patients were taking a Fibrate but did not have a decreased HDL-C level until Rosiglitazone was introduced.

Given the findings of the 3 cases from the medical literature and the Canadian case, in patients prescribed Rosiglitazone, it would be advisable to measure baseline HDL-C and triglyceride levels and check them again shortly after the start of therapy.

Source: Health Canada, 2005


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