What medications are recommended for treating high triglycerides?

Medications for High Triglycerides

For patients with high triglycerides, fibrates (fenofibrate or gemfibrozil) are the first-line pharmacological treatment when triglycerides are ≥500 mg/dL, while for moderate hypertriglyceridemia (150-499 mg/dL), statins remain first-line with fibrates as adjunctive therapy. 1

Classification and Treatment Approach

For Severe Hypertriglyceridemia (≥500 mg/dL)

1. First-line treatment: Fibrates

   • Fenofibrate (preferred): 54-160 mg daily 1
   • Gemfibrozil: 600 mg twice daily 2, 1

   Fenofibrate is preferred over gemfibrozil when combined with statins due to lower risk of myopathy 1

2. Alternative options:

   • Niacin (nicotinic acid): For patients who cannot tolerate fibrates 3
   • Omega-3 fatty acids (fish oils): 2-4 g daily 2

For Moderate Hypertriglyceridemia (200-499 mg/dL)

1. First-line treatment: Improved glycemic control plus statin 2
2. Second-line treatment: Statin plus fibrate 2
3. Third-line treatment: Statin plus nicotinic acid 2

Efficacy of Medications

Fibrates

• Fenofibrate reduces triglycerides by approximately 38-50% 4, 5
• Real-world studies show about 49% of patients reach triglyceride levels <150 mg/dL after fenofibrate treatment 4
• Fenofibrate also reduces total cholesterol by 13-24% and LDL-C by 21-25% 6, 5

Niacin

• Indicated as adjunctive therapy for severe hypertriglyceridemia when patients don't respond to dietary efforts 3
• Can effectively increase HDL cholesterol levels 2
• Low doses (≤2 g/day) may have minimal impact on glycemic control 2

Omega-3 Fatty Acids

• For elevated triglycerides, doses of 2-4 g/day may be used 2
• Considered a Class IIb recommendation (may be reasonable) 2

Special Considerations

Renal Impairment

• For fenofibrate:
  • Normal or mild-moderate CKD: 96 mg/day
  • Moderate CKD (eGFR 30-59 mL/min): 48 mg/day
  • Severe CKD (eGFR <30 mL/min): Avoid use 1, 7

Combination Therapy

• When combining with statins:
  • Fenofibrate is preferred over gemfibrozil due to lower risk of myopathy 1
  • Monitor for muscle symptoms and check creatine phosphokinase if symptoms develop 1
  • Keep statin doses relatively low when using combination therapy 2

Monitoring

• Baseline and periodic monitoring recommended for:
  • Liver function tests
  • Renal function
  • Creatine phosphokinase (CPK)
  • Lipid profile 1

Lifestyle Modifications

Essential lifestyle modifications should be implemented before or alongside pharmacological therapy:

1. Improved glycemic control (particularly effective for triglyceride reduction) 2
2. Weight reduction if overweight/obese 2, 1
3. Dietary modifications:
   • Reduced intake of saturated fats (<7% of total calories)
   • Reduced cholesterol (<200 mg/day)
   • Reduced trans fat (<1% of energy) 2
4. Regular physical activity 2
5. Reduced or eliminated alcohol consumption (especially important with very high triglycerides) 2, 1

Common Pitfalls and Caveats

1. Myopathy risk: The combination of statins with fibrates increases risk of myopathy. Fenofibrate has lower risk than gemfibrozil when combined with statins 1

2. Renal function: Always assess renal function before starting fibrates and adjust dosing accordingly 7

3. Diabetes impact: Niacin may worsen glycemic control in diabetic patients and should be used with caution 2

4. Pancreatitis risk: Triglyceride levels >1000 mg/dL significantly increase risk of pancreatitis and require aggressive treatment 1

5. Treatment response: Female sex, non-diabetic status, and lower baseline triglycerides are associated with better response to fenofibrate 4