Treatment of Elevated Triglycerides

Classification Determines Treatment Strategy

The treatment approach for hypertriglyceridemia is determined by the severity of triglyceride elevation, with lifestyle modifications forming the foundation for all levels, while pharmacologic therapy selection depends on whether the primary goal is preventing pancreatitis (triglycerides ≥500 mg/dL) or reducing cardiovascular risk (triglycerides 150-499 mg/dL). 1, 2, 3

Triglyceride Classification and Risk Assessment

Before initiating treatment, classify the severity 1, 2, 3:

Normal: <150 mg/dL
Mild: 150-199 mg/dL (cardiovascular risk-enhancing factor)
Moderate: 200-499 mg/dL (increased cardiovascular risk)
Severe: 500-999 mg/dL (14% risk of acute pancreatitis)
Very Severe: ≥1,000 mg/dL (dramatic pancreatitis risk)

Identify and Address Secondary Causes FIRST

Before starting any medication, evaluate and correct reversible factors 1, 2, 4:

Uncontrolled diabetes: Check HbA1c and fasting glucose—optimizing glycemic control can reduce triglycerides by 20-50% independent of lipid medications 1, 2
Hypothyroidism: Measure TSH and treat before expecting full response to lipid therapy 1, 3
Excessive alcohol: Even 1 ounce daily increases triglycerides by 5-10%; complete abstinence is mandatory for levels ≥500 mg/dL 1, 2, 4
Medications: Discontinue or substitute thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, or antipsychotics if possible 1, 4
Renal/liver disease: Assess creatinine, eGFR, AST, and ALT as these conditions worsen hypertriglyceridemia and affect medication dosing 1, 2

Lifestyle Modifications (All Severity Levels)

Weight Loss and Physical Activity

Target 5-10% body weight reduction—this produces a 20% decrease in triglycerides and is the single most effective intervention 1, 2, 3
Engage in ≥150 minutes/week of moderate-intensity aerobic activity (or 75 minutes/week vigorous activity), which reduces triglycerides by approximately 11% 1, 2, 3

Dietary Modifications Based on Severity

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

Restrict added sugars to <6% of total daily calories
Limit total dietary fat to 30-35% of total calories
Restrict saturated fats to <7% of calories, replacing with monounsaturated or polyunsaturated fats
Consume ≥2 servings (8+ ounces) per week of fatty fish (salmon, trout, sardines)
Increase soluble fiber to >10 g/day from oats, beans, and vegetables

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

Restrict total dietary fat to 20-25% of total calories
Eliminate all added sugars completely
Complete alcohol abstinence

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

Implement very low-fat diet (10-15% of total calories)
In some cases, consider extreme fat restriction (<5% of calories) until triglycerides fall below 1,000 mg/dL

Pharmacologic Therapy Algorithm

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

Initiate fenofibrate immediately to prevent acute pancreatitis, regardless of LDL-C levels or cardiovascular risk. 1, 2, 3, 4

Fenofibrate dosing 4:
- Initial dose: 54-160 mg daily with meals
- For normal renal function (eGFR ≥60): Start 54 mg daily, may titrate to 160 mg daily based on response at 4-8 week intervals
- For mild-moderate renal impairment (eGFR 30-59): Start 54 mg daily, do not exceed this dose
- Contraindicated if eGFR <30 or on dialysis
Expected effect: 30-50% triglyceride reduction 1, 2, 3
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, 3

For Moderate Hypertriglyceridemia (200-499 mg/dL)

If 10-year ASCVD risk ≥7.5%, elevated LDL-C, or established cardiovascular disease: 1, 2, 3

Initiate moderate-to-high intensity statin therapy as first-line (e.g., atorvastatin 10-40 mg or rosuvastatin 5-20 mg daily)
Statins provide 10-30% dose-dependent triglyceride reduction plus proven cardiovascular mortality benefit
Target LDL-C <100 mg/dL (or <70 mg/dL for very high-risk patients)
Target non-HDL-C <130 mg/dL (calculated as total cholesterol minus HDL-C)

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

Add icosapent ethyl 2g twice daily (total 4g/day) IF the patient has:
- Established cardiovascular disease OR
- Diabetes with ≥2 additional cardiovascular risk factors
Icosapent ethyl demonstrated a 25% reduction in major adverse cardiovascular events (number needed to treat = 21) 1, 2
Monitor for increased risk of atrial fibrillation (3.1% vs 2.1% on placebo) 1

Alternative if icosapent ethyl criteria not met: 1, 2

Consider fenofibrate 54-160 mg daily as add-on therapy
When combining fenofibrate with statins, use lower statin doses to minimize myopathy risk, particularly in patients >65 years or with renal disease

For Mild Hypertriglyceridemia (150-199 mg/dL)

If 10-year ASCVD risk ≥7.5%: 1, 2

Consider moderate-intensity statin therapy, as persistently elevated triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor
Statins provide 10-30% triglyceride reduction plus proven cardiovascular benefit

If ASCVD risk 5-7.5%: 1

Engage in patient-clinician discussion regarding statin initiation
Prioritize aggressive lifestyle modifications for 3 months before pharmacotherapy

Critical Safety Considerations

Combination Therapy Warnings

Fenofibrate is preferred over gemfibrozil when combining with statins—gemfibrozil has significantly higher myopathy risk and should be avoided 1, 2
When combining fenofibrate with statins: Use lower statin doses (e.g., atorvastatin 10-20 mg maximum), monitor creatine kinase levels at baseline and follow-up, and take fenofibrate in the morning and statins in the evening to minimize peak dose concentrations 1, 2
Monitor renal function within 3 months after fenofibrate initiation and every 6 months thereafter; discontinue if eGFR persistently decreases to <30 mL/min/1.73 m² 1

Niacin Limitations

Niacin should generally not be used as it showed no cardiovascular benefit when added to statin therapy in the AIM-HIGH trial, with increased risk of new-onset diabetes and gastrointestinal disturbances 1, 5
Niacin may be considered for severe hypertriglyceridemia (≥500 mg/dL) when fibrates are contraindicated 5

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, 2
Monitor liver function tests and creatine kinase if fibrates are added, particularly at baseline and 3 months after initiation 1, 2
Once goals are achieved: Follow-up every 6-12 months 1

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, 2
Do NOT start with statin monotherapy when triglycerides are ≥500 mg/dL—statins provide only 10-30% triglyceride reduction, insufficient for preventing pancreatitis 1, 2
Do NOT use over-the-counter fish oil supplements expecting cardiovascular benefit—only prescription omega-3 formulations (icosapent ethyl) have proven cardiovascular outcomes 1
Do NOT discontinue statins in favor of fibrate monotherapy for patients with cardiovascular risk—statins provide proven mortality benefit through LDL-C reduction 1, 2
Do NOT overlook glycemic control in diabetic patients—optimizing glucose control can be more effective than additional lipid medications 1, 2

What is the treatment approach for a patient with hypertriglyceridemia?

Help us tailor your experience