From the Guidelines
Treatment for isolated elevated triglycerides should be initiated when levels exceed 500 mg/dL to reduce the risk of acute pancreatitis, as recommended by the most recent guidelines 1. When considering the management of hypertriglyceridemia, it's crucial to evaluate the patient's overall cardiovascular risk and address any secondary causes of elevated triglycerides.
- For patients with triglyceride levels between 150-499 mg/dL, treatment should focus on lifestyle modifications, such as weight loss, limiting alcohol intake, and increasing physical activity, as well as addressing underlying causes and reducing cardiovascular risk 1.
- First-line treatment includes lifestyle modifications, and for levels above 500 mg/dL, pharmacological therapy is typically recommended alongside lifestyle changes.
- Fibrates, omega-3 fatty acids, niacin, and statins may be used depending on the patient's overall lipid profile and cardiovascular risk.
- In severe cases (>1000 mg/dL), a very low-fat diet and combination therapy might be required to reduce the risk of acute pancreatitis. The guidelines from 2025 1 provide the most up-to-date recommendations for the management of hypertriglyceridemia, emphasizing the importance of addressing lifestyle factors, secondary causes, and considering medical therapy to reduce the risk of pancreatitis and cardiovascular events.
- Key recommendations include:
- Evaluating for secondary causes of hypertriglyceridemia and considering medical therapy for levels ≥500 mg/dL 1.
- Addressing lifestyle factors, secondary factors, and medications that raise triglycerides for levels >150 mg/dL 1.
- Considering the addition of icosapent ethyl for individuals with ASCVD or other cardiovascular risk factors on a statin with managed LDL cholesterol but elevated triglycerides (150–499 mg/dL) 1.
From the FDA Drug Label
The effects of fenofibrate on serum triglycerides were studied in two randomized, double-blind, placebo-controlled clinical trials of 147 hypertriglyceridemic patients Patients were treated for eight weeks under protocols that differed only in that one entered patients with baseline TG levels of 500 mg/dL to 1,500 mg/dL, and the other TG levels of 350 mg/dL to 500 mg/dL
Table 5: Effects of Fenofibrate in Patients with Severe Hypertriglyceridemia Study 1 Placebo Fenofibrate Baseline TG levels 350 to 499 mg/dL N Baseline (Mean) Endpoint (Mean) % Change (Mean) N Baseline (Mean) Endpoint (Mean) % Change (Mean) Triglycerides 28 449 450 -0.5 27 432 223 -46.2*
Study 2 Placebo Fenofibrate Baseline TG levels 500 to 1500 mg/dL N Baseline (Mean) Endpoint (Mean) % Change (Mean) N Baseline (Mean) Endpoint (Mean) % Change (Mean) Triglycerides 44 710 750 7.2 48 726 308 -54.5*
The treatment of isolated elevated triglycerides with fenofibrate should be considered at baseline TG levels of 350 mg/dL to 1,500 mg/dL or higher, as these levels were used in the clinical trials to study the effects of fenofibrate on serum triglycerides 2.
- Key points:
- Fenofibrate decreased triglycerides by 46.2% in patients with baseline TG levels of 350 to 499 mg/dL.
- Fenofibrate decreased triglycerides by 54.5% in patients with baseline TG levels of 500 to 1,500 mg/dL. It is essential to note that the decision to treat isolated elevated triglycerides should be made on a case-by-case basis, considering the individual patient's risk factors and medical history.
From the Research
Treatment of Isolated Elevated Triglycerides
The decision to treat isolated elevated triglycerides depends on the level of hypertriglyceridemia and the patient's overall cardiovascular risk.
- For patients with mildly elevated triglyceride levels (150-499 mg/dL), treatment typically starts with dietary changes and physical activity to lower cardiovascular risk 3.
- Severely elevated triglyceride levels (≥500 mg/dL) increase the risk of pancreatitis, and treatment should be initiated to reduce this risk 3, 4, 5.
- The American family physician recommends calculating a patient's 10-year risk of atherosclerotic cardiovascular disease to determine the role of medications in treating high triglyceride levels 3.
Treatment Options
Several treatment options are available for managing hypertriglyceridemia, including:
- Therapeutic lifestyle changes (TLC), such as a low saturated fat, carbohydrate-controlled diet, combined with alcohol reduction, smoking cessation, and regular aerobic exercise 6.
- Omega-3 fatty acids, which can lower triglyceride levels significantly, especially at high doses (≥2 g/day) 7.
- Fibrates, which are initially considered for isolated hypertriglyceridemia 6.
- Statins, which are preferred when elevated low-density lipoprotein levels accompany hypertriglyceridemia 6.
- Niacin, which can be considered for patients with low HDL levels and hypertriglyceridemia 6.
- Combination therapy may be necessary in recalcitrant cases 6.
Triglyceride Levels and Treatment
The following triglyceride levels are associated with specific treatment approaches:
- 150-499 mg/dL: Dietary changes and physical activity to lower cardiovascular risk 3.
- ≥500 mg/dL: Immediate use of triglyceride-lowering agents to reduce the risk of pancreatitis 4, 5.
- ≥1000 mg/dL: Insulin infusion and plasmapheresis should be considered if triglyceride levels remain elevated despite conservative management of acute pancreatitis 3.