When should elevated triglycerides be treated?

When to Treat Triglycerides

Treatment Thresholds Based on Severity

Treat triglycerides immediately with fibrates when levels reach ≥500 mg/dL to prevent acute pancreatitis, regardless of cardiovascular risk or LDL levels. 1, 2

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

• Initiate fenofibrate 54-160 mg daily immediately as first-line therapy when triglycerides are ≥500 mg/dL, as this level carries a 14% risk of acute pancreatitis and represents a medical emergency. 1, 2

• At triglyceride levels ≥1,000 mg/dL, implement extreme dietary fat restriction (<5% of total calories) alongside fenofibrate until levels fall below 1,000 mg/dL. 1, 2

• The primary goal at this threshold is preventing pancreatitis—cardiovascular risk reduction becomes secondary. 1, 3

• Do not start with statin monotherapy when triglycerides are ≥500 mg/dL, as statins provide only 10-30% triglyceride reduction, which is insufficient for pancreatitis prevention. 1

Moderate Hypertriglyceridemia (200-499 mg/dL)

• For patients with 10-year ASCVD risk ≥7.5% or diabetes (age 40-75 years), initiate moderate-to-high intensity statin therapy as first-line, which provides 10-30% triglyceride reduction plus proven cardiovascular mortality benefit. 1, 2

• Target non-HDL-C <130 mg/dL as a secondary goal when triglycerides are in this range. 4, 1

• If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, consider adding icosapent ethyl 2-4g daily for patients with established cardiovascular disease OR diabetes with ≥2 additional risk factors. 1, 2

Mild Hypertriglyceridemia (150-199 mg/dL)

• For patients with 10-year ASCVD risk ≥7.5%, consider initiating statin therapy, as persistently elevated nonfasting triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor. 1, 2

• Aggressive lifestyle modifications are first-line for this category: target 5-10% weight loss (produces 20% triglyceride reduction), restrict added sugars to <6% of calories, and engage in ≥150 minutes/week of moderate-intensity aerobic activity. 1, 5

• Pharmacologic therapy is generally not indicated unless other cardiovascular risk factors are present. 2, 3

Critical Secondary Causes to Address First

Before initiating any triglyceride-lowering medication, aggressively evaluate and treat secondary causes, as addressing these can reduce triglycerides by 20-70% independent of lipid medications. 1, 5

• Uncontrolled diabetes mellitus: Check HbA1c immediately—poor glycemic control is often the primary driver of severe hypertriglyceridemia. Optimizing glucose control can dramatically reduce triglycerides independent of lipid medications. 1, 5

• Hypothyroidism: Measure TSH, as this common secondary cause must be treated before expecting full response to lipid-lowering therapy. 1, 5

• Excessive alcohol consumption: Even 1 ounce daily increases triglycerides by 5-10%. Complete abstinence is mandatory for triglycerides ≥500 mg/dL. 1, 5

• Medications that raise triglycerides: Review for thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, and antipsychotics—discontinue or substitute if possible. 1

Lifestyle Modifications: The Foundation

Implement aggressive lifestyle modifications immediately for all patients with triglycerides ≥150 mg/dL, as these interventions can reduce triglycerides by 20-50% and are the most effective non-pharmacologic approach. 1, 5, 6

• Weight loss of 5-10% produces a 20% decrease in triglycerides—the single most effective lifestyle intervention. 1, 5

• Restrict added sugars to <6% of total daily calories (eliminate completely if triglycerides ≥500 mg/dL), as sugar intake directly increases hepatic triglyceride production. 1, 5

• Limit total dietary fat to 30-35% of calories for mild-moderate hypertriglyceridemia; restrict to 20-25% for severe (500-999 mg/dL); restrict to 10-15% for very severe (≥1,000 mg/dL). 1, 5

• Restrict saturated fats to <7% of total energy intake, replacing with monounsaturated or polyunsaturated fats. 1, 5

• Engage in ≥150 minutes/week of moderate-intensity aerobic activity, which reduces triglycerides by approximately 11%. 1, 5

Common Pitfalls to Avoid

• Do not delay fibrate therapy while attempting lifestyle modifications alone when triglycerides are ≥500 mg/dL—pharmacologic intervention is mandatory at this threshold. 1

• Do not discontinue statins in favor of fibrate monotherapy for patients with cardiovascular risk or established disease, as statins provide proven mortality benefit through LDL-C reduction. 1

• Do not use gemfibrozil when combining with statins—fenofibrate has a significantly better safety profile with lower myopathy risk. 1

• Do not use over-the-counter fish oil supplements expecting cardiovascular benefit—only prescription icosapent ethyl has proven cardiovascular outcomes benefit. 1, 3

• Do not delay statin therapy while attempting lifestyle modifications alone in high-risk patients (diabetes age 40-75,10-year ASCVD risk ≥7.5%)—pharmacotherapy and lifestyle optimization should occur simultaneously. 1

Monitoring Strategy

• Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications. 1, 5

• Reassess lipids 4-8 weeks after initiating or adjusting pharmacologic therapy. 1

• When combining fenofibrate with statins, monitor creatine kinase levels and muscle symptoms, particularly in patients >65 years or with renal disease. 1

• Monitor renal function within 3 months after fenofibrate initiation and every 6 months thereafter. 1