Fibrates

Fibrates, also known as fibric acid derivatives, are a class of lipid-modifying medications used to treat hypertriglyceridemia and mixed dyslipidemia. They act as agonists of peroxisome proliferator-activated receptor alpha (PPAR-α), which increases transcription of genes involved in fatty acid oxidation and lipoprotein lipase activity. This leads to reduced hepatic production of triglyceride-rich VLDL particles and enhanced clearance of triglycerides, with modest effects on raising high-density lipoprotein (HDL) cholesterol.

Clinically, fibrates are most effective at lowering triglycerides, with typical reductions in the 20–50% range, and can produce small increases in HDL cholesterol. LDL cholesterol may be unchanged or modestly decreased. They are particularly useful in patients with severe hypertriglyceridemia to reduce pancreatitis risk and can be used in mixed dyslipidemia when triglycerides are prominent. They may be used alone or in combination with statins in some patients, but combination therapy requires careful monitoring because of interaction risks.

Safety and tolerability: Common side effects include gastrointestinal symptoms, rash, and gallstone formation. More serious concerns include myopathy and liver injury, especially when fibrates are used with statins. Renal function influences dosing because most fibrates are excreted by the kidneys; dose adjustment is necessary in chronic kidney disease. The combination of certain fibrates (notably gemfibrozil) with statins carries a higher risk of myopathy, and some guidelines prefer fenofibrate when a fibrate is combined with a statin. Contraindications include active liver disease and severe renal impairment. Other agents in the same class include fenofibrate, bezafibrate, and newer selective PPAR-α modulators such as pemafibrate in some regions.