What medications are used to treat elevated triglycerides?

Medications for Elevated Triglycerides

For patients with elevated triglycerides, fibrates are the first-line pharmacological treatment, especially when triglyceride levels exceed 500 mg/dL and risk of pancreatitis is present. 1

Classification of Hypertriglyceridemia

• Mild to moderate: 150-499 mg/dL
• Severe: 500-999 mg/dL
• Very severe: ≥1000 mg/dL

First-Line Approach: Lifestyle Modifications

Before initiating medication, address underlying factors:

1. Weight loss for overweight/obese patients (most effective intervention)
2. Dietary modifications:
   • Reduce simple carbohydrates
   • Limit alcohol consumption
   • For severe hypertriglyceridemia (≥500 mg/dL): very low-fat diet (10-15% of calories)
   • For very severe hypertriglyceridemia (≥1000 mg/dL): extreme fat restriction (<5% of calories)
3. Regular physical activity
4. Address secondary causes:
   • Uncontrolled diabetes
   • Hypothyroidism
   • Renal/liver disease
   • Medications (corticosteroids, antiretrovirals, etc.)

Medication Options by Triglyceride Level

For Severe Hypertriglyceridemia (≥500 mg/dL)

Primary goal: Reduce pancreatitis risk

1. Fibrates (first-line therapy) 1

   • Gemfibrozil 600 mg twice daily
   • Fenofibrate 54-160 mg daily
   • Typically reduce triglycerides by 35-50%
   • Caution: Increased risk of myopathy when combined with statins

2. Prescription Omega-3 Fatty Acids 1

   • Icosapent ethyl (pure EPA) 2g twice daily
   • Omega-3 acid ethyl esters (EPA+DHA)
   • Typically reduce triglycerides by 20-50%

3. Niacin (alternative option) 1

   • Caution: May worsen insulin resistance
   • Side effects include flushing

For Moderate Hypertriglyceridemia (150-499 mg/dL)

Primary goal: Reduce cardiovascular risk

1. Statins 1

   • Modest triglyceride-lowering effect (10-15%)
   • First choice when elevated LDL-C is also present
   • Target non-HDL cholesterol level of 30 mg/dL higher than LDL goal

2. Icosapent ethyl 1

   • Consider for patients with ASCVD or cardiovascular risk factors on statin therapy with controlled LDL but elevated triglycerides (135-499 mg/dL)
   • Shown to reduce cardiovascular events by 25%

3. Fibrates, niacin, or omega-3 fatty acids (alone or in combination) 1

   • Consider when statin therapy is insufficient

Combination Therapy Considerations

• Statin + fibrate: Generally not recommended due to increased risk of myopathy 1

  • If used, avoid gemfibrozil with statins; fenofibrate has lower interaction risk
  • Take fibrate in morning and statin in evening

• Statin + niacin: Not recommended due to lack of cardiovascular benefit and increased stroke risk 1

• Statin + omega-3 fatty acids: Safer combination option 1

Special Considerations

1. Diabetes: Aggressive glycemic control can improve triglyceride levels 1

2. Very high triglycerides (>2000 mg/dL):

   • Immediate dietary fat restriction
   • Consider combination therapy
   • Eliminate alcohol completely

3. Monitoring:

   • Follow triglyceride levels 4-12 weeks after initiating therapy
   • Monitor for muscle symptoms with fibrates and statins
   • Monitor liver enzymes with fibrates

Common Pitfalls

1. Using statins alone for severe hypertriglyceridemia (insufficient for triglyceride reduction)

2. Overlooking secondary causes of hypertriglyceridemia

3. Inadequate dietary counseling, particularly regarding simple carbohydrates and alcohol

4. Inappropriate combination therapy (statin + gemfibrozil) increasing myopathy risk

5. Failing to recognize pancreatitis risk when triglycerides exceed 500 mg/dL

The medication choice should be guided by triglyceride level, cardiovascular risk, and presence of other lipid abnormalities, with fibrates being the clear first choice for severe hypertriglyceridemia to prevent pancreatitis.