Should we treat hypertriglyceridemia in patients with diabetes to prevent cardiovascular complications?

Abstract

Hypertriglyceridemia is a common lipid abnormality in type 2 diabetes mellitus and is a hallmark of atherogenic dyslipidemia, which is also characterized by low HDL cholesterol levels and a predominance of small, dense LDL particles. Although LDL cholesterol remains the primary therapeutic target for cardiovascular prevention, persistent hypertriglyceridemia reflects a significant residual cardiovascular risk, even in patients receiving appropriate statin therapy.

The primary therapeutic goals remain optimization of glycemic control, weight reduction when appropriate, regular physical activity, restriction of alcohol consumption, and treatment of secondary causes of hypertriglyceridemia. At the same time, intensive statin therapy continues to be the pharmacological intervention with the greatest proven impact on reducing cardiovascular risk in people with diabetes. When triglyceride levels are ≥500 mg/dL, treatment has a different objective: the prevention of acute pancreatitis. In this setting, fibrates, omega-3 fatty acids, and a very low-fat diet are appropriate interventions, together with intensive metabolic control.

Cardiovascular prevention represents a different clinical scenario. In patients with established atherosclerotic cardiovascular disease or with diabetes at high cardiovascular risk who are receiving statin therapy and have persistent triglyceride levels between 150 and 499 mg/dL, the only treatment with consistent evidence of reducing cardiovascular events is icosapent ethyl (IPE) at a dose of 4 g/day. In contrast, other omega-3 fatty acid formulations and pemafibrate have not demonstrated cardiovascular benefit, confirming that not all triglyceride-lowering therapies produce the same clinical effect. Current American Diabetes Association (ADA) recommendations reflect this evidence and consider the use of icosapent ethyl in selected patients.

In conclusion, the answer is yes, but with different therapeutic objectives depending on the clinical context. Severe hypertriglyceridemia should be treated to prevent acute pancreatitis, whereas moderate hypertriglyceridemia should initially be managed through lifestyle modification, optimization of diabetes control, and statin therapy. Only in patients at high cardiovascular risk with persistently elevated triglyceride levels despite statin treatment is there robust evidence supporting the addition of icosapent ethyl to reduce cardiovascular events.