What is the most effective way to decrease severely elevated triglyceride (hypertriglyceridemia) levels?

From the Guidelines

To decrease very high triglyceride levels, the most effective approach is to combine lifestyle modifications with medication therapy, prioritizing a very low-fat diet and prescription-strength omega-3 fatty acids for levels above 500 mg/dL, as recommended by the most recent guidelines 1.

Key Lifestyle Modifications

• Reduce intake of simple carbohydrates, sugars, and alcohol
• Increase physical activity to at least 150 minutes of moderate exercise weekly
• Adopt a Mediterranean-style diet rich in omega-3 fatty acids from fatty fish, nuts, and olive oil
• For extremely high levels (>1000 mg/dL), a very low-fat diet (<15% of calories) may be temporarily required, as suggested by the 2021 ACC expert consensus decision pathway 1

Medication Therapy

• Prescription-strength omega-3 fatty acids like icosapent ethyl (Vascepa) 2 grams twice daily or omega-3 ethyl esters (Lovaza) 4 grams daily are typically recommended for very high levels (>500 mg/dL) 1
• Fibrates such as fenofibrate (145 mg daily) or gemfibrozil (600 mg twice daily) are also effective first-line medications
• Statins may be added, particularly if LDL cholesterol is also elevated, as recommended by the 2022 standards of medical care in diabetes 1

Additional Considerations

• Weight loss of 5-10% of body weight can significantly reduce triglycerides
• Tight control of blood sugar in diabetic patients can also help reduce triglycerides
• Immediate medical attention is necessary to prevent pancreatitis for extremely high levels (>1000 mg/dL), as emphasized by the 2021 ACC expert consensus decision pathway 1 and the 2022 standards of medical care in diabetes 1

From the FDA Drug Label

Fenofibrate tablets are indicated as adjunctive therapy to diet to reduce elevated low-density lipoprotein cholesterol (LDL-C), total cholesterol (Total-C), Triglycerides and apolipoprotein B (Apo B), and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia. Fenofibrate tablets are also indicated as adjunctive therapy to diet for treatment of adult patients with severe hypertriglyceridemia.

The most effective way to decrease very high triglyceride levels is to use fenofibrate as an adjunctive therapy to diet.

• The initial dose of fenofibrate tablet is 160 mg once daily for primary hypercholesterolemia or mixed dyslipidemia.
• The initial dose for severe hypertriglyceridemia is 54 mg per day to 160 mg per day, with dosage individualized according to patient response.
• Dietary therapy is the initial treatment for dyslipidemia, and patients should continue this diet during treatment with fenofibrate tablets 2, 2.

From the Research

Effective Ways to Decrease Very High Triglyceride Levels

• Lifestyle modifications, such as cessation of alcohol consumption, reduced intake of rapidly metabolized carbohydrates, weight loss, and blood sugar control, are the most effective ways to lower triglyceride levels 3
• Therapeutic lifestyle changes, including a healthy diet and regular exercise, should be the initial approach for managing hypertriglyceridemia 4, 5
• Dietary changes, such as lowering carbohydrate intake and increasing fat and protein intake, can help lower triglyceride levels 5
• Moderate- to high-intensity physical activity can also lower triglyceride levels and improve body composition and exercise capacity 5

Pharmacological Treatment

• Statins can be considered for patients with high triglyceride levels who have borderline or intermediate risk of atherosclerotic cardiovascular disease 5
• For patients at high risk who continue to have high triglyceride levels despite statin use, high-dose icosapent (purified eicosapentaenoic acid) can reduce cardiovascular mortality 5
• Fibrates, omega-3 fatty acids, or niacin should be considered for patients with severely elevated triglyceride levels to reduce the risk of pancreatitis 4, 5
• Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin for reducing triglyceride levels 6

Special Considerations

• Patients with very high triglyceride levels (≥500 mg/dL) are at increased risk of acute pancreatitis and require immediate treatment with triglyceride-lowering agents 4, 5
• Patients with acute pancreatitis associated with hypertriglyceridemia may require insulin infusion and plasmapheresis if triglyceride levels remain high despite conservative management 5