The diabetes world is well acquainted with the risks of hypercholesteremia and the benefits of statins and other lipid-lowering therapies. Elevated triglycerides are less familiar.

“Triglycerides are often ignored, partly because people don’t know what to do about them,” said Savitha Subramanian, MD, Medical Director of the Lipid Clinic and Associate Professor of Metabolism, Endocrinology, and Nutrition at the University of Washington. “People should know that there are now drugs being developed and are on the market for hypertriglyceridemia. These new drugs improve the quality of life for people with very high triglycerides, especially with pancreatitis. People can die from pancreatitis, and hypertriglyceridemia is the number three cause of pancreatitis.”

Dr. Subramanian will explore the newest therapies for severe hypertriglyceridemia during the session, The Elephant in the Room—How to Address Hypertriglyceridemia in Diabetes?, on Monday, June 23, from 3:15–4:15 p.m., in Room W185 A–D of the McCormick Place Convention Center. One drug, olezarsen, was approved by the U.S. Food and Drug Administration (FDA) in late 2024. The second drug, plozasiran, is under review for FDA approval.

Olezarsen was originally developed for familial chylomicronemia syndrome (FCS), a heredity form of hypertriglyceridemia that affects one to two individuals per million and is usually diagnosed in childhood or adolescence. Zahid Ahmad, MD, Associate Professor of Endocrinology, University of Texas Southwestern Medical Center, will discuss the genetics of hypertriglyceridemia and diabetes.

Individuals with FCS typically have triglycerides in the 1,000s and higher and are usually seen by specialists, Dr. Subramanian said. Endocrinologists and diabetologists are more likely to see individuals with both diabetes and elevated triglycerides. These patients typically have obesity and type 2 diabetes and likely have a genetic predisposition to dyslipidemia that can be exacerbated by environmental and lifestyle factors.

Triglycerides are metabolized by lipoprotein lipase, explained Robert S. Rosenson, MD, Professor of Cardiology at the Ichan School of Medicine at Mount Sinai and Fuster Heart Hospital, and Director of the Metabolism and Lipids Program at Mount Sinai Health System. Insulin resistance downregulates lipoprotein lipase activity, which can lead to hypertriglyceridemia and other abnormal lipid levels.

“More severe insulin-resistant states are associated with higher triglycerides and lower HDL cholesterol,” Dr. Rosenson said. “Triglycerides are carried in very low-density lipoproteins and also in chylomicrons, ultra-low-density lipoproteins. People with poorly managed diabetes typically have triglyceride levels over 880 mg/dL due to the underlying insulin resistance and mixed hyperlipidemia.”

Statins can lower LDL cholesterol, he continued, but have only modest effects on triglycerides. Many individuals who take high-intensity statins can still have elevated triglycerides as well as an elevated risk for pancreatitis. Fibrates, icosapent, and other existing agents have limited triglyceride-lowering effects and are less effective in people with hypertension.

Pancreatitis can lead to both hospitalization and damage to the beta cells that can effectively halt endogenous insulin production. Both olezarsen and plozasiran lowered triglyceride levels by about 70% in clinical trials and the risk of acute pancreatitis by about 80%.

“This is a game-changer for people with severe, uncontrolled hyper triglycerides,” Dr. Rosenson said. “For the first time we have a class of triglyceride-lowering therapy that are more than twofold more effective than existing medications and also can reduce acute pancreatitis.”

On-demand access to recorded presentations will be available to registered participants following the conclusion of the 85^th Scientific Sessions, from June 25–August 25.