What medications are used to treat elevated triglyceride levels (hypertriglyceridemia)?

Medications for Elevated Triglycerides

For severe hypertriglyceridemia (≥500 mg/dL), fenofibrate 54-160 mg daily is the first-line medication to prevent acute pancreatitis, providing 30-50% triglyceride reduction; for moderate hypertriglyceridemia (150-499 mg/dL) with elevated cardiovascular risk, statins are first-line providing 10-30% reduction, with icosapent ethyl 2-4g daily added if triglycerides remain ≥150 mg/dL on maximally tolerated statin therapy in patients with established cardiovascular disease or diabetes with additional risk factors. 1, 2, 3

Treatment Algorithm by Triglyceride Level

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

Immediate pharmacologic intervention is mandatory to prevent acute pancreatitis, regardless of cardiovascular risk. 1

• Fenofibrate 54-200 mg daily is first-line therapy, initiated immediately before addressing LDL cholesterol, reducing triglycerides by 30-50% 1, 2, 3
• Statins provide only 10-30% triglyceride reduction and are insufficient at this level—do not start with statin monotherapy when triglycerides are ≥500 mg/dL 1
• Once triglycerides fall below 500 mg/dL with fenofibrate, reassess LDL-C and add statin therapy if LDL-C is elevated or cardiovascular risk is high 1
• Prescription omega-3 fatty acids (2-4g daily) can be added as adjunctive therapy to fenofibrate if triglycerides remain persistently elevated 1

Moderate Hypertriglyceridemia (150-499 mg/dL)

Statins are first-line pharmacologic therapy if 10-year ASCVD risk is ≥7.5% or if LDL-C is elevated. 1

• Moderate-to-high intensity statin therapy (atorvastatin 10-40 mg or rosuvastatin 5-20 mg daily) provides 10-30% dose-dependent triglyceride reduction with proven cardiovascular benefit 1
• Target non-HDL-C <130 mg/dL as a secondary goal when triglycerides are 200-499 mg/dL 4, 1
• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, add icosapent ethyl 2g twice daily for patients with established cardiovascular disease OR diabetes with ≥2 additional risk factors 1, 5
• Icosapent ethyl provides a 25% reduction in major adverse cardiovascular events (number needed to treat = 21) 1, 5

Mild Hypertriglyceridemia (150-199 mg/dL)

• For patients with 10-year ASCVD risk 7.5% to <20%, consider moderate-intensity statin therapy if persistently elevated nonfasting triglycerides ≥175 mg/dL 1
• For ASCVD risk 5% to <7.5%, engage in patient-clinician discussion regarding statin initiation 1

Specific Medication Details

Fibrates (Fenofibrate Preferred)

• Fenofibrate 54-160 mg daily reduces triglycerides by 30-50% and increases HDL-C by 6-12% 4, 2
• Fenofibrate has a better safety profile than gemfibrozil when combined with statins—gemfibrozil should be avoided due to significantly higher myopathy risk 1
• 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
• Adjust fenofibrate dose based on renal function 1

Statins

• Provide 10-30% dose-dependent triglyceride reduction in patients with elevated levels 4, 1
• Should be restricted to patients with both high LDL cholesterol and high triglycerides for triglyceride management 1
• High-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) provide ≥50% LDL-C reduction with additional triglyceride lowering 1

Prescription Omega-3 Fatty Acids

• Icosapent ethyl (purified EPA) 2g twice daily is indicated as adjunct to maximally tolerated statin therapy for patients with triglycerides ≥150 mg/dL and established cardiovascular disease OR diabetes with ≥2 additional risk factors 1, 5
• Icosapent ethyl is the only triglyceride-lowering therapy FDA-approved for cardiovascular risk reduction 1
• Omega-3 carboxylic acid and omega-3-acid ethyl esters (EPA + DHA combinations) are FDA-approved only for severe hypertriglyceridemia (≥500 mg/dL) as adjunct to diet, not for cardiovascular risk reduction 1
• Monitor for increased risk of atrial fibrillation (3.1% vs 2.1% hospitalization rate) 1
• Over-the-counter fish oil supplements are not equivalent to prescription formulations and should not be substituted 1

Niacin

• Provides 20-50% triglyceride reduction with immediate-release formulation and 10-30% with extended-release 4
• Niacin should generally not be used, as it showed no cardiovascular benefit when added to statin therapy, with increased risk of new-onset diabetes and gastrointestinal disturbances 1
• Can be considered at restricted dose of 2g/day in select cases, but fibrates are preferred 1

Ezetimibe

• Provides only 5-10% triglyceride reduction—insufficient as primary triglyceride-lowering therapy 4
• Provides additional 13-20% LDL-C reduction when added to statins with proven cardiovascular benefit 1

Critical Pitfalls to Avoid

• Do not delay fibrate initiation while attempting lifestyle modifications alone in patients with triglycerides ≥500 mg/dL—pharmacologic therapy is mandatory to prevent pancreatitis 1
• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL—initiate fibrates or niacin before LDL-lowering therapy 1
• Do not use gemfibrozil when combining with statins—fenofibrate has significantly lower myopathy risk 1
• Do not ignore secondary causes including uncontrolled diabetes, hypothyroidism, excessive alcohol intake, and medications that raise triglycerides (thiazides, beta-blockers, estrogen, corticosteroids, antiretrovirals, antipsychotics) 1
• Do not use bile acid sequestrants when triglycerides are >200 mg/dL—they are relatively contraindicated and may raise triglyceride levels 4, 1
• Do not combine high-dose statins with fibrates without dose adjustment—use lower statin doses to minimize myopathy risk 1

Special Considerations

• Aggressively optimize glycemic control in diabetic patients—poor glucose control is often the primary driver of severe hypertriglyceridemia and may be more effective than additional lipid medications 1
• Complete alcohol abstinence is mandatory for patients with severe hypertriglyceridemia (≥500 mg/dL) to prevent hypertriglyceridemic pancreatitis 1
• Monitor creatine kinase levels and muscle symptoms when using combination therapy, particularly at baseline and 3 months after initiation 1
• Reassess fasting lipid panel in 4-8 weeks after initiating or adjusting therapy 1