What medication is used to treat high triglycerides (hypertriglyceridemia)?

Medication for Hypertriglyceridemia (TG 317 mg/dL)

Primary Recommendation

For a triglyceride level of 317 mg/dL (moderate hypertriglyceridemia), statins remain the first-line pharmacologic therapy if cardiovascular risk is elevated, with fibrates or prescription omega-3 fatty acids (icosapent ethyl) reserved as add-on therapy if triglycerides remain elevated despite statin therapy and lifestyle optimization. 1

Treatment Algorithm Based on Triglyceride Level and Risk

Step 1: Address Secondary Causes First

Before initiating any pharmacologic therapy, evaluate and correct:

• Uncontrolled diabetes (optimize glycemic control with target HbA1c <7%) 2, 1
• Excessive alcohol intake (limit or completely avoid) 2, 1
• Hypothyroidism (check TSH and treat if elevated) 1
• Medications that raise triglycerides (estrogens, beta-blockers, thiazides, corticosteroids) 1
• Obesity (target 5-10% weight loss, which can reduce triglycerides by 20-70%) 1

Step 2: Implement Aggressive Lifestyle Modifications

• Dietary changes: Restrict added sugars to <6% of total daily calories and limit total fat to 30-35% of calories 1
• Physical activity: At least 150 minutes/week of moderate-intensity aerobic activity 1
• Weight reduction: 5-10% weight loss is the most effective intervention 1
• Low-carbohydrate diets are more effective than low-fat diets for triglyceride reduction 3

Step 3: Determine Cardiovascular Risk and Medication Strategy

For TG 317 mg/dL (moderate hypertriglyceridemia, 200-499 mg/dL):

If 10-year ASCVD risk ≥7.5% OR established cardiovascular disease:

• Initiate moderate- to high-intensity statin therapy as first-line pharmacologic treatment 2, 1
• Statins provide 10-30% triglyceride reduction while simultaneously lowering LDL-C 1, 4
• Target non-HDL-C <130 mg/dL 2, 1

If triglycerides remain >200 mg/dL after 3 months of statin therapy plus optimized lifestyle:

• Add icosapent ethyl (prescription EPA) 2-4 g/day for patients with established cardiovascular disease or diabetes with ≥2 additional risk factors 2, 1
• Icosapent ethyl reduces cardiovascular mortality (NNT = 111 over 5 years) 3
• Monitor for increased risk of atrial fibrillation 1

Alternative add-on option:

• Fenofibrate can be considered if triglycerides remain significantly elevated, but combination statin-fibrate therapy has NOT been shown to improve cardiovascular outcomes in most patients 2
• The ACCORD trial showed no benefit of fenofibrate plus simvastatin versus simvastatin alone for cardiovascular events 2
• Exception: Consider fenofibrate for men with TG ≥204 mg/dL AND HDL-C ≤34 mg/dL 2

Critical Distinction: When Fibrates Are First-Line

Fibrates become first-line therapy ONLY when triglycerides reach ≥500 mg/dL to prevent acute pancreatitis, NOT for your patient's level of 317 mg/dL 2, 1, 3

At TG ≥500 mg/dL:

• Immediate fenofibrate 54-200 mg daily BEFORE addressing LDL cholesterol 1
• Fibrates reduce triglycerides by 30-50% 2, 5
• Prescription omega-3 fatty acids (2-4 g/day) can be added as adjunctive therapy 2, 1

Medications to Avoid

Do NOT use:

• Niacin plus statin: No cardiovascular benefit beyond statin alone, may increase stroke risk 2
• Gemfibrozil plus statin: Higher risk of rhabdomyolysis compared to fenofibrate 2
• Bile acid sequestrants: Contraindicated when triglycerides >200 mg/dL as they can worsen hypertriglyceridemia 2, 1

Monitoring and Safety

When using statin therapy:

• Recheck fasting lipid panel in 6-12 weeks 1
• Monitor for myopathy symptoms (muscle pain, weakness) 2
• Be aware of drug interactions with CYP3A4 inhibitors (macrolides, azole antifungals, calcium channel blockers) that increase myopathy risk 2

If adding fenofibrate to statin:

• Use fenofibrate (NOT gemfibrozil) to minimize myopathy risk 2
• Take fibrate in morning, statin in evening to minimize peak dose overlap 2
• Monitor creatine kinase levels at baseline and with symptoms 2, 1
• Use lower statin doses when combining with fibrates 1

Common Pitfalls to Avoid

• Do not start with fibrates for moderate hypertriglyceridemia (200-499 mg/dL) when cardiovascular risk reduction is the goal—statins are superior 1, 4
• Do not delay addressing secondary causes (especially diabetes control)—optimizing glycemic control can be more effective than adding medications 1
• Do not use over-the-counter fish oil as a substitute for prescription omega-3 fatty acids—they are not equivalent 1
• Do not ignore lifestyle modifications—they remain foundational even when medications are initiated 1, 3