Lipid-Lowering Medications Demonstrate Cardiometabolic Benefits in Populations with High-Risk Diabetes
Once-Monthly Injection Reduced Triglycerides and the Risk of Acute Pancreatitis; Bi-Weekly Injection Lowered "Bad" Cholesterol and Cardiovascular Events
People living with diabetes are nearly 75% more likely to develop acute pancreatitis (AP) and are nearly twice as likely to develop heart disease or stroke. This underscores the need to target risk factors for these conditions, including harmful triglycerides (a type of fat carried in your blood that your body uses for energy) and atherosclerosis (plaque buildup in the arteries that can cause heart disease), often caused by "bad" cholesterol (LDL-C).
Phase 3 Data Highlights Potential of Olezarsen in Reducing Triglycerides
Researchers conducted two phase 3 randomized controlled trials, CORE-TIMI 72a (617 patients) and CORE2-TIMI 72b (446 patients), to evaluate the effectiveness of olezarsen, a targeted medication designed to lower dangerously high triglyceride levels in people whose bodies have trouble clearing fat from the blood. Patients with high blood fat levels (severe hypertriglyceridemia) were treated with olezarsen (at 50mg or 80mg) or placebo for 12 months. The primary endpoint was placebo-adjusted percent change in triglyceridemia (TG) levels at six months. Secondary endpoints included AP events.
Olezarsen reduced excess blood fat and helped lower the risk of pancreatitis in patients with diabetes. Of the total 1,063 patients, 673 (63%) had a history of diabetes (median A1C 7.3%; diabetes duration nine years; 25% on glucagon-like peptide-1 receptor agonists [GLP-1RAs] and 37% on insulin). Baseline TG levels were similar in patients with diabetes (median 784 mg/dL) compared to those without diabetes (807 mg/dL; p=0.43), but those with diabetes history were more likely to have had prior AP (21% vs. 14%; p=0.005). Compared with placebo, the 50 mg and 80 mg doses of olezarsen reduced TGs by 57.4% (95% CI 48.6-66.2) and 64.8% (95% CI 56.0-73.6) in patients with diabetes. Compared with placebo, olezarsen treatment reduced the risk of AP by 81% in this population, from an incidence rate of 8.46 per 100 patient-years to 1.55 per 100 patient-years. These findings translate to a number needed to treat to prevent one AP event over one year of 15.
"When a patient has high levels of triglycerides in their blood, combined with diabetes, one of the most immediate concerns is acute pancreatitis, which can lead to serious short- and long-term complications," said
CORE-OLE (NCT05681351), an open-label extension study of CORE-TIMI 72a and CORE2-TIMI 72b, is ongoing. The results from CORE-OLE is expected to provide insights on the long-term efficacy and safety of olezarsen in this high-risk population.
Simultaneously Published Data Shows Evolocumab Can
The VESALIUS-CV trial is a double-blind, randomized, placebo-controlled, multicenter study to evaluate the impact of evolocumab on major cardiovascular events in patients at high cardiovascular risk without prior myocardial infarction or stroke with an elevated LDL-C ≥90 mg/dL while on an optimized lipid-lowering therapy. Evolocumab is an injection that helps the body remove bad cholesterol from the blood. Researchers randomized patients with high "bad" cholesterol (LDL-C >90mg/dL) and atherosclerosis or high-risk diabetes (based on a history of retinopathy or chronic kidney disease, on daily insulin, or diabetes duration of 10 years or greater) but no prior heart attack or stroke, to those who received evolocumab (140mg) or the placebo. The dual primary endpoints were coronary heart disease death, heart attack (myocardial infarction) or ischemic stroke (3-P MACE), and the previously listed plus ischemia-driven arterial revascularization (4-P MACE).
As simultaneously published in Diabetes Care®, results of a pre-specified subgroup analysis from the VESALIUS-CV trial showed evolocumab reduced the rate of cardiovascular events in patients with high-risk diabetes. Of the overall study population of 12,257 patients, 6,002 (49%) had high-risk diabetes, with a median age of 66 and 50% female. Evolocumab lowered LDL-C by more than 50%, down to 45 mg/dL. After a median follow-up of 4.6 years, there was a 29% reduction in 3-P MACE in patients with high-risk diabetes treated with evolocumab, compared to the placebo group. The use of evolocumab decreased 4-P MACE by 21%. The risk of a heart attack was lowered by 35% and lower mortality with evolocumab was observed. Findings were consistent regardless of qualifying atherosclerosis, baseline LDL-C, statin intensity, and sodium-glucose cotransporter 2 inhibitors (SGLT2i) or GLP-1RA use.
"We know that individuals living with diabetes, even if they do not have known clogged arteries, are at high risk for cardiovascular disease," said
The authors note further analyses in the VESALIUS-CV trial are underway to better understand the clinical benefit across other subgroups.
Research Presentation Details
Yu Mi Kang , MD, PhD, MPH- Oral presentation: Newer Concepts in Management of Diabetes and Hypertriglyceridemia
Saturday, June 6 from3:15-3:30 p.m. CT - Ernest N. Morial Convention Center, Hall E-3 (Level 1)
Evolocumab Reduces CV Events in Patients with High-Risk Diabetes: Results from the VESALIUS-CV Trial
Lawrence A. Leiter , MD, FRCPC, FACP, FACE, FAHA, FACC, professor of medicine, University of Toronto,Toronto, Canada - Oral presentation: Short Talks from Abstracts, Clinical Updates on PCSK9 Inhibition and Triglyceride-Related CVD
Sunday, June 7 from3:45-4:00 p.m. CT Ernest N. Morial Convention Center ,Room 200 (Level 2)
About American Diabetes Association's 2026 Scientific Sessions
The ADA's 2026 Scientific Sessions, the world's largest scientific meeting focused on diabetes research, prevention, and care, will be held in
About American Diabetes Association
The American Diabetes Association (ADA) is the nation's leading voluntary health organization fighting to end diabetes and helping people thrive. This year, the ADA celebrates 85 years of driving discovery and research to prevent, manage, treat, and ultimately cure diabetes—and we're not stopping. There are over 155 million Americans living with diabetes or prediabetes. Through advocacy, program development, and education, we're fighting for them all. To learn more or to get involved, visit us at diabetes.org or call 1-800-DIABETES (800-342-2383). Join us in the fight on Facebook (American Diabetes Association), Spanish Facebook (Asociación Americana de la Diabetes), LinkedIn (American Diabetes Association), and Instagram (@AmDiabetesAssn). To learn more about how we are advocating for everyone affected by diabetes, visit us on X (@AmDiabetesAssn). (@AmDiabetesAssn). To learn more about how we are advocating for everyone affected by diabetes, visit us on X (@AmDiabetesAssn).
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SOURCE American Diabetes Association
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