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Fibrate derivatives are lipid-lowering medications that primarily target triglycerides rather than LDL cholesterol. Common agents include gemfibrozil, fenofibrate, and fenofibric acid. While their use has declined with the widespread adoption of statins, fibrates remain an important option for patients with severe hypertriglyceridemia, particularly to reduce the risk of acute pancreatitis rather than for routine cardiovascular risk reduction.
Fibrates work by activating PPAR-alpha, which increases lipoprotein lipase activity and enhances the clearance of triglyceride-rich lipoproteins. This leads to significant reductions in triglycerides, modest increases in HDL cholesterol, and variable effects on LDL cholesterol. Because they are not strong LDL-lowering agents, fibrates should not replace statins in patients who require LDL reduction, but they can be effective in select clinical scenarios when triglycerides are the primary concern.
From a safety standpoint, fibrates are generally well tolerated but require careful monitoring. Common concerns include gastrointestinal side effects, liver enzyme elevations, gallstone risk, and muscle toxicity, especially when combined with statins. Gemfibrozil carries a higher risk of drug interactions, while fenofibrate is usually preferred if combination therapy is necessary. Appropriate patient selection, lab monitoring, and lifestyle counseling are essential to maximize benefit and minimize harm when using fibrate derivatives.
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