What is the best medication to lower hypertriglyceridemia?

Best Medications for Lowering Triglycerides

Fibrates (fenofibrate or gemfibrozil) are the most effective first-line medications for lowering triglycerides, particularly in severe hypertriglyceridemia (≥500 mg/dL), with fenofibrate preferred over gemfibrozil when combination therapy with statins is needed. 1

Treatment Algorithm Based on Triglyceride Levels

For Severe Hypertriglyceridemia (≥500 mg/dL)

1. First-line therapy: Fibrates

   • Fenofibrate 54-160 mg daily 2
   • Gemfibrozil 600 mg twice daily 2
   • Fenofibrate is preferred when combined with statins due to lower risk of myopathy 1

2. Alternative options:

   • Prescription omega-3 fatty acids (2-4 g/day) 2, 3
   • Icosapent ethyl for patients with established ASCVD or diabetes plus risk factors 2

3. Adjunctive measures:

   • Optimize glycemic control in patients with diabetes 2
   • Severely restrict dietary fat (<10% of calories) 1
   • Restrict alcohol intake 2

For Moderate Hypertriglyceridemia (150-499 mg/dL)

1. Primary focus: Statin therapy if indicated by ASCVD risk 2, 1
2. Add-on therapy if triglycerides remain elevated despite statin:
   • Fibrates (fenofibrate preferred with statins) 2, 1
   • Prescription omega-3 fatty acids 3
   • Niacin (with caution in diabetes) 2

Efficacy of Medications

1. Fibrates:

   • Most potent triglyceride-lowering agents, reducing levels by 30-50% 2, 4
   • In severe hypertriglyceridemia (500-1500 mg/dL), fenofibrate reduced triglycerides by 54.5% 4
   • Also increase HDL-C by 10-20% 4

2. Prescription Omega-3 Fatty Acids:

   • Reduce triglycerides by approximately 30-45% at 4 g/day dosing 3
   • EPA-only formulations (icosapent ethyl) have cardiovascular outcome benefits 3
   • Do not increase LDL-C when used as monotherapy 3

3. Niacin:

   • Reduces triglycerides by up to 30% 2
   • Most effective agent for raising HDL-C 1
   • Use with caution in diabetes due to potential worsening of glycemic control 2, 1

4. Statins:

   • Moderate triglyceride-lowering effect (especially at higher doses) 2
   • Primary choice when LDL-C is also elevated 2
   • High-intensity statins can lower triglycerides by 20-30% 1

Important Considerations and Precautions

• Combination therapy risks: The combination of statins with fibrates increases risk of myopathy; fenofibrate has lower risk than gemfibrozil when combined with statins 2, 1

• Diabetes considerations: Optimize glycemic control first, as this can significantly reduce triglyceride levels 2

• Monitoring: Check lipid panels 4-8 weeks after initiating therapy 1

• Pancreatitis risk: Urgent treatment needed for triglycerides >1000 mg/dL to prevent pancreatitis 5

• Cardiovascular risk: In high-risk patients with elevated triglycerides despite statin therapy, icosapent ethyl has been shown to reduce cardiovascular events 2, 3

Non-Pharmacological Approaches

While medications are the focus of this response, lifestyle modifications remain essential:

• Reduce carbohydrate intake (especially refined carbohydrates) 5
• Increase omega-3 fatty acid consumption 2
• Moderate-to-high intensity physical activity 5
• Weight reduction 2
• Alcohol restriction 2

Fibrates remain the cornerstone of treatment for severe hypertriglyceridemia, with prescription omega-3 fatty acids as valuable alternatives. The choice of medication should be guided by the severity of triglyceride elevation, presence of other lipid abnormalities, and individual patient factors such as diabetes status and cardiovascular risk.