What is the treatment for high triglycerides (hypertriglyceridemia)?

Treatment of High Triglycerides (Hypertriglyceridemia)

The treatment approach depends entirely on your triglyceride level: for severe hypertriglyceridemia (≥500 mg/dL), immediately start fenofibrate 54-160 mg daily to prevent acute pancreatitis; for moderate levels (200-499 mg/dL), optimize lifestyle modifications and consider statins if cardiovascular risk is elevated or LDL-C is high; for mild elevation (150-199 mg/dL), focus on lifestyle changes first and add statin therapy only if 10-year cardiovascular disease risk is ≥7.5%. 1, 2, 3

Classification-Based Treatment Algorithm

Severe to Very Severe Hypertriglyceridemia (≥500 mg/dL)

Immediate pharmacologic intervention is mandatory to prevent acute pancreatitis, which occurs in 14% of patients at this level. 1, 4

• Start fenofibrate 54-160 mg daily immediately as first-line therapy, before addressing LDL cholesterol. 1, 5 Fenofibrate reduces triglycerides by 30-50%. 1, 2
• Implement extreme dietary fat restriction to 20-25% of total calories for levels 500-999 mg/dL, or 10-15% for levels ≥1,000 mg/dL. 1, 3
• Eliminate all added sugars and alcohol completely. 1, 3, 5 Even 1 ounce of alcohol daily increases triglycerides by 5-10%, and alcohol can precipitate hypertriglyceridemic pancreatitis at these levels. 1
• Aggressively evaluate and treat secondary causes, particularly uncontrolled diabetes and hypothyroidism, as optimizing glucose control can dramatically reduce triglycerides independent of lipid medications. 1, 2, 5
• Once triglycerides fall below 500 mg/dL, reassess LDL-C and add statin therapy if LDL-C is elevated or cardiovascular risk is high. 1, 2

Moderate Hypertriglyceridemia (200-499 mg/dL)

Lifestyle modifications are the foundation, with pharmacotherapy guided by cardiovascular risk and LDL-C levels. 1, 2, 4

• If 10-year ASCVD risk is ≥7.5% or LDL-C is elevated, initiate moderate-to-high intensity statin therapy (atorvastatin 20-40 mg or rosuvastatin 10-20 mg daily). 1 Statins provide 10-30% dose-dependent triglyceride reduction plus proven cardiovascular benefit. 1, 2, 6
• Target a non-HDL-C goal of <130 mg/dL (calculated as total cholesterol minus HDL-C). 1, 2
• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, add prescription omega-3 fatty acids (icosapent ethyl 2-4g daily) for patients with established cardiovascular disease or diabetes with ≥2 additional risk factors. 1, 4 Icosapent ethyl reduces major adverse cardiovascular events by 25%. 1
• Alternatively, consider fenofibrate 54-160 mg daily if omega-3 criteria are not met and triglycerides remain persistently elevated. 1, 2

Mild Hypertriglyceridemia (150-199 mg/dL)

Focus on lifestyle interventions first, with pharmacotherapy reserved for patients with elevated cardiovascular risk. 1, 3, 4

• If 10-year ASCVD risk is ≥7.5%, consider moderate-intensity statin therapy. 1
• If ASCVD risk is 5% to <7.5%, engage in patient-clinician discussion regarding statin initiation, as persistently elevated triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor. 1
• Implement lifestyle modifications as detailed below before considering pharmacotherapy. 2, 3, 4

Essential Lifestyle Interventions (All Severity Levels)

Weight Loss and Physical Activity

• Target 5-10% body weight reduction, which produces a 20% decrease in triglycerides—the single most effective lifestyle intervention. 1, 2, 3 In some patients, weight loss can reduce triglycerides by up to 50-70%. 1
• Engage in ≥150 minutes/week of moderate-intensity aerobic activity (or 75 minutes/week vigorous activity), which reduces triglycerides by approximately 11%. 1, 3, 7

Dietary Modifications

• Restrict added sugars to <6% of total daily calories for mild-moderate hypertriglyceridemia, <5% for severe levels, or eliminate completely for very severe levels. 1, 3 Sugar intake directly increases hepatic triglyceride production. 1
• Limit total fat to 30-35% of total calories for mild-moderate levels, 20-25% for severe levels, or 10-15% for very severe levels. 1, 3
• Restrict saturated fats to <7% of total energy intake, replacing with monounsaturated or polyunsaturated fats. 1, 8
• Consume ≥2 servings per week of fatty fish (salmon, trout, sardines) rich in omega-3 fatty acids. 1, 7
• Increase soluble fiber to >10 g/day from sources like oats, beans, and vegetables. 1, 8
• Limit or completely avoid alcohol, especially with severe hypertriglyceridemia where complete abstinence is mandatory. 1, 3, 5

Critical Secondary Causes to Address

Before initiating or escalating pharmacotherapy, evaluate and treat these conditions: 1, 2, 5

• Uncontrolled diabetes mellitus—optimize glycemic control, as poor glucose control is often the primary driver of severe hypertriglyceridemia. 1, 5
• Hypothyroidism—check TSH and treat if elevated. 1, 8
• Excessive alcohol intake—counsel on reduction or elimination. 5, 8
• Medications that raise triglycerides—thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals. 1, 5 Consider discontinuation or substitution if possible.
• Renal disease and liver disease—assess kidney and liver function. 1, 8

Combination Therapy Safety Considerations

When combining fenofibrate with statins, use lower statin doses (atorvastatin 10-20 mg maximum) to minimize myopathy risk, particularly in patients >65 years or with renal disease. 1, 2 Fenofibrate has a significantly better safety profile than gemfibrozil when combined with statins. 1, 9

Monitor for myopathy with baseline and follow-up creatine kinase levels and muscle symptoms when using combination therapy. 1, 2

Monitor for increased risk of atrial fibrillation with prescription omega-3 fatty acids at doses of 2-4g daily. 1

Monitoring and Follow-Up

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications. 1, 2, 3
• Reassess lipids 4-8 weeks after initiating or adjusting pharmacotherapy. 1, 5
• Withdraw therapy in patients who do not have an adequate response after two months of treatment with the maximum recommended dose. 5

Common Pitfalls to Avoid

• Do not delay fibrate therapy while attempting lifestyle modifications alone in patients with triglycerides ≥500 mg/dL—pharmacologic therapy is mandatory to prevent pancreatitis. 1, 4
• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL, as statins provide only 10-30% triglyceride reduction and are insufficient for preventing pancreatitis at this level. 1
• Do not use gemfibrozil when combining with statins—fenofibrate has a significantly lower myopathy risk. 1, 9
• Do not ignore secondary causes, particularly uncontrolled diabetes and hypothyroidism, as treating these conditions can be more effective than additional medications. 1, 5, 8
• Do not use over-the-counter fish oil supplements as a substitute for prescription omega-3 formulations, as they are not equivalent. 1