What are the medications for managing elevated triglycerides?

Medications for Managing Elevated Triglycerides

The primary medications for managing elevated triglycerides are fibric acid derivatives (fenofibrate and gemfibrozil), omega-3 fatty acids (particularly icosapent ethyl), and high-dose statins, with fibrates being the most potent triglyceride-lowering agents available. 1, 2

First-Line Pharmacological Options

Fibric Acid Derivatives

• Fenofibrate and gemfibrozil are the most potent triglyceride-lowering agents, reducing levels by up to 50%. 3, 2
• For severe hypertriglyceridemia (≥500 mg/dL), fibrates are indicated to reduce the risk of pancreatitis. 1, 4
• Gemfibrozil is FDA-approved for treating very high triglyceride elevations (Types IV and V hyperlipidemia) that present a risk of pancreatitis. 4
• Fenofibrate is preferred over gemfibrozil when combining with statins due to lower risk of myopathy. 3, 2
• Fenofibrate increases HDL cholesterol levels without affecting glycemic control in diabetic patients. 3

Omega-3 Fatty Acids

• Prescription-grade omega-3 fatty acids (particularly icosapent ethyl) reduce triglycerides by up to 40%. 2
• Icosapent ethyl is FDA-approved as adjunct therapy to reduce triglyceride levels in adults with severe hypertriglyceridemia (≥500 mg/dL). 5
• In individuals with ASCVD or cardiovascular risk factors on a statin with managed LDL cholesterol but elevated triglycerides (150-499 mg/dL), adding icosapent ethyl can reduce cardiovascular risk. 1

Statins

• High-dose statins are moderately effective at lowering triglycerides in hypertriglyceridemic patients who also have high LDL cholesterol. 1
• Statins can reduce mean triglyceride levels by up to 18%, or up to 43% in patients with triglyceride levels ≥273 mg/dL. 6

Treatment Algorithm by Triglyceride Level

Triglycerides 150-499 mg/dL (Mild to Moderate)

• Address lifestyle factors (obesity, metabolic syndrome), secondary factors (diabetes, liver/kidney disease, hypothyroidism), and medications that raise triglycerides. 1
• If on statin therapy with managed LDL but persistent elevation, consider adding icosapent ethyl. 1
• For diabetic patients, improved glycemic control plus high-dose statin is first choice. 1

Triglycerides ≥500 mg/dL (Severe)

• Evaluate for secondary causes and initiate medical therapy to reduce pancreatitis risk. 1
• Fibric acid derivatives (fenofibrate or gemfibrozil) are first-line pharmacological treatment. 3, 2, 4
• Consider prescription omega-3 fatty acids as alternative or adjunct therapy. 2, 5

Triglycerides ≥1,000 mg/dL (Very Severe)

• Severe dietary fat restriction (<10% of calories) in addition to pharmacological therapy is necessary. 1, 3
• Immediate fibrate therapy is indicated. 4

Special Populations

Diabetic Patients

• Optimizing glycemic control is the first priority before initiating lipid-lowering therapy. 1, 3, 2
• After glycemic control, fibric acid derivatives (fenofibrate preferred) are recommended. 1, 3
• For combined hyperlipidemia, improved glycemic control plus high-dose statin is first choice, followed by statin plus fenofibrate if needed. 1, 3

Combination Therapy Considerations

Statin Plus Fibrate

• Fenofibrate is strongly preferred over gemfibrozil when combining with statins due to significantly lower myopathy risk. 3, 2
• Statin plus fibrate combination therapy has not been shown to improve ASCVD outcomes and is generally not recommended. 1
• The combination increases risk of myositis and rhabdomyolysis, particularly with gemfibrozil. 1
• Monitor renal function closely, as risk increases with renal insufficiency. 1

Statin Plus Niacin

• Statin plus niacin combination has not shown additional cardiovascular benefit above statin alone, may increase stroke risk, and is generally not recommended. 1
• Niacin can reduce triglycerides by up to 30% but should be used with caution. 2
• In diabetic patients, this combination may significantly worsen hyperglycemia and requires frequent glucose monitoring if used. 1

Monitoring and Safety

Fenofibrate

• Evaluate renal function before starting, within 3 months after initiation, and every 6 months thereafter. 3
• Limit dose to 54 mg/day for patients with eGFR 30-59 mL/min/1.73 m². 3
• Avoid if eGFR <30 mL/min/1.73 m². 3
• Monitor lipid levels 4-12 weeks after initiation and every 3-12 months thereafter. 3

Common Pitfalls

• Do not use fibrates as monotherapy for Type IIa patients with elevated LDL cholesterol only, as potential toxicity risks outweigh benefits. 4
• Do not combine gemfibrozil with statins due to high myopathy risk; use fenofibrate instead. 3, 2
• Ensure lifestyle modifications (weight loss, increased physical activity, alcohol moderation) are implemented before or concurrent with pharmacotherapy. 1