A Monthly Injection for Severe Triglycerides Made Pancreatitis Attacks Far Rarer

CATEGORY: HEART & CIRCULATION

Can pulling triglycerides down keep people out of the hospital with pancreatitis? That question drove two identical trials in 1,063 adults with severely elevated triglycerides. The answer was yes. Monthly injections of olezarsen cut attacks of acute pancreatitis by 85% compared with placebo: 7 attacks among treated patients, 22 among those on placebo.¹

When Blood Fat Turns Into an Emergency

Triglycerides are the main fat circulating in blood. Past 500 mg/dL, doctors call the condition severe hypertriglyceridemia. At that level the danger shifts to the pancreas. Fat-clogged blood can inflame it suddenly, causing acute pancreatitis, a painful inflammation of the digestive gland that usually means a hospital stay and can turn deadly. Until this year, no drug was approved specifically to lower that risk. Olezarsen was built to be that drug. It silences a liver protein called apoC-III so the body can clear triglycerides faster.

Two Trials Run as Mirror Images

CORE and CORE2 enrolled 617 and 446 adults with fasting triglycerides of 500 mg/dL or higher. Study pharmacies dealt each person monthly olezarsen at 50 mg or 80 mg, or a matching placebo shot, with no one the wiser. The planned main outcome was the triglyceride change at six months, and pancreatitis attacks were counted and verified across both trials. Triglycerides fell 49% to 72% from baseline depending on dose and trial, and more than 85% of treated patients got under the 500 mark.¹ The pancreatitis result came out to 1.01 attacks per 100 patient-years on the drug versus 6.23 on placebo. Among the highest-risk patients, those starting near 900 or with a previous attack, treating four people prevented one attack.

The Fine Print Sits in the Liver

Overall side effects matched placebo, but two signals deserve the attention they’re getting. Liver fat rose with dose: a jump of at least 5 percentage points showed up in 27% of people on the lower dose and 40% on the higher one, with unknown long-term meaning. Blood sugar control also slipped slightly, about a quarter point of HbA1c, the three-month blood sugar average. The trials were funded by the drug’s maker, and the FDA approved olezarsen for severe hypertriglyceridemia in June 2026, making it the first treatment cleared to reduce pancreatitis risk in these patients.

Key Takeaways

• Monthly olezarsen cut triglycerides by roughly half to nearly three quarters and reduced acute pancreatitis attacks 85% (1.01 versus 6.23 attacks per 100 patient-years) in two placebo-controlled trials of adults with severe hypertriglyceridemia.
• Liver fat and blood sugar rose modestly on treatment, the long-term record is short, and the evidence applies to triglycerides of 500 mg/dL and up, not to ordinary mildly elevated readings.

References

1. Marston NA, et al. Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk. The New England Journal of Medicine. 2026;394(5):429–441. link