What is the treatment for high triglycerides (hypertriglyceridemia)?

Treatment of High Triglycerides

For patients with high triglycerides, treatment should be stratified by severity: lifestyle modifications are foundational for all levels, but pharmacologic intervention with fenofibrate is mandatory for triglycerides ≥500 mg/dL to prevent acute pancreatitis, while moderate elevations (200-499 mg/dL) warrant statin therapy if cardiovascular risk is elevated or LDL-C is high. 1, 2, 3

Classification and Risk Assessment

Triglyceride levels determine treatment urgency 1, 2, 3:

• Normal: <150 mg/dL
• Mild: 150-199 mg/dL (cardiovascular risk marker)
• Moderate: 200-499 mg/dL (increased cardiovascular risk)
• Severe: 500-999 mg/dL (pancreatitis risk ~14%)
• Very Severe: ≥1,000 mg/dL (high pancreatitis risk)

Before initiating treatment, evaluate for secondary causes including excessive alcohol intake, uncontrolled diabetes, hypothyroidism, renal disease, liver disease, and medications (thiazides, beta-blockers, estrogen, corticosteroids, antiretrovirals, antipsychotics). 1, 2, 3, 4, 5 Poor glycemic control in diabetic patients is often the primary driver of severe hypertriglyceridemia and must be aggressively optimized first. 1

Lifestyle Interventions (All Patients)

Weight loss is the single most effective lifestyle intervention, with 5-10% body weight reduction producing a 20% decrease in triglycerides; some patients achieve up to 50-70% reduction. 1, 2, 3, 6, 7

Dietary Modifications by Severity Level

For mild-moderate hypertriglyceridemia (150-499 mg/dL): 1, 2, 3

• Restrict added sugars to <6% of total daily calories (sugar directly increases hepatic triglyceride production)
• Limit total fat to 30-35% of total daily calories
• Restrict saturated fats to <7% of total energy intake, replacing with monounsaturated or polyunsaturated fats
• Increase soluble fiber to >10 g/day
• Consume ≥2 servings per week of fatty fish (salmon, trout, sardines)

For severe hypertriglyceridemia (500-999 mg/dL): 1, 2, 3

• Restrict total dietary fat to 20-25% of total daily calories
• Eliminate all added sugars completely

For very severe hypertriglyceridemia (≥1,000 mg/dL): 1, 2, 3

• Implement very low-fat diet (10-15% of total calories)
• In some cases, restrict fat to <5% of total calories until triglycerides fall below 1,000 mg/dL
• Eliminate all added sugars and alcohol completely

Alcohol and Exercise

Complete alcohol abstinence is mandatory for patients with triglycerides ≥500 mg/dL to prevent hypertriglyceridemic pancreatitis; even 1 ounce daily increases triglycerides by 5-10%. 1, 2, 3, 4, 6 For mild-moderate elevations, limit or drastically reduce alcohol consumption. 1, 5

Engage in at least 150 minutes per week of moderate-intensity aerobic activity (or 75 minutes per week of vigorous activity), which reduces triglycerides by approximately 11%. 1, 2, 3

Pharmacologic Therapy Algorithm

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

Initiate fenofibrate 54-160 mg daily immediately as first-line therapy to prevent acute pancreatitis, regardless of LDL-C levels or cardiovascular risk. 1, 2, 3, 4 Fenofibrate reduces triglycerides by 30-50%. 1, 8, 5

• Dosing: Start at 54 mg daily in patients with mild-moderate renal impairment; titrate to 160 mg daily based on response and renal function. 4
• Monitoring: Reassess lipid panel at 4-8 week intervals. 1, 4
• Goal: Rapidly reduce triglycerides to <500 mg/dL to eliminate pancreatitis risk, then further reduce to <200 mg/dL for cardiovascular risk reduction. 1

Once triglycerides fall below 500 mg/dL, reassess LDL-C and consider adding statin therapy if LDL-C is elevated or cardiovascular risk is high. 1, 2

Moderate Hypertriglyceridemia (200-499 mg/dL)

For patients with elevated LDL-C or 10-year ASCVD risk ≥7.5%, initiate moderate-to-high intensity statin therapy as first-line treatment. 1, 2, 6 Statins provide 10-30% dose-dependent triglyceride reduction and proven cardiovascular benefit. 1, 8

If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, consider adding: 1, 2

• Icosapent ethyl 2-4 g daily for patients with established cardiovascular disease OR diabetes with ≥2 additional risk factors (provides 25% reduction in major adverse cardiovascular events)
• Fenofibrate 54-160 mg daily if icosapent ethyl criteria are not met (provides 30-50% triglyceride reduction)

Target non-HDL-C <130 mg/dL (calculated as total cholesterol minus HDL-C) as a secondary goal. 1, 2

Mild Hypertriglyceridemia (150-199 mg/dL)

For patients with 10-year ASCVD risk ≥7.5%, consider moderate-intensity statin therapy, as persistently elevated triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor. 1, 2

For patients with ASCVD risk 5% to <7.5%, engage in patient-clinician discussion regarding statin initiation. 1

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, 8 Fenofibrate is preferred over gemfibrozil when combining with statins due to significantly lower myopathy risk. 1, 8, 5

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

Special Populations and Considerations

Diabetic patients: Optimize glycemic control aggressively, as this can be more effective than additional lipid medications in reducing severe hypertriglyceridemia. 1, 2, 3 Target HgA1C <7%. 1

Renal impairment: Initiate fenofibrate at 54 mg daily and titrate cautiously; avoid in severe renal impairment. 4

Elderly patients: Base dose selection on renal function. 4

Monitoring and Follow-up

Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications, and 4-8 weeks after initiating or adjusting pharmacotherapy. 1, 2, 3 Therapy should be withdrawn in patients who do not have an adequate response after two months of treatment with the maximum recommended dose of fenofibrate 160 mg once daily. 4

Critical Pitfalls to Avoid

• Do not delay fibrate therapy while attempting lifestyle modifications alone in patients with triglycerides ≥500 mg/dL—pharmacologic intervention is mandatory to prevent pancreatitis. 1, 2
• 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. 1
• Do not overlook secondary causes, particularly uncontrolled diabetes and hypothyroidism, as treating these conditions can dramatically reduce triglycerides independent of lipid medications. 1, 2, 3, 4, 5
• Do not use gemfibrozil when combining with statins due to significantly higher myopathy risk compared to fenofibrate. 1, 8, 5
• Do not use bile acid sequestrants when triglycerides are >200 mg/dL, as they are relatively contraindicated. 1