A new investigational medication, DR10624, has demonstrated the ability to reduce triglyceride levels by more than 60% in patients with severe hypertriglyceridemia and to significantly decrease liver fat, according to late-breaking research presented at the American Heart Association’s Scientific Sessions 2025. The Phase 2, double-blind, placebo-controlled trial involved 79 adults with triglyceride levels between 500 and 2,000 mg/dL, a condition associated with increased risks of pancreatitis, cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease (MASLD).
DR10624 is a first-of-its-kind triple agonist that activates FGF21, glucagon, and GLP-1 receptors, which are involved in regulating fat and sugar metabolism. Over 12 weeks, patients receiving weekly subcutaneous injections of DR10624 experienced dramatic reductions in triglycerides: 74.5% with the 12.5 mg dose, 66.2% with 25 mg, and 68.9% with the 50 mg titration dose, compared to an 8.0% reduction in the placebo group. Additionally, 89.5% of treated patients achieved triglyceride levels below 500 mg/dL, versus 25% in the placebo group.
The drug also significantly improved other lipid parameters, including total cholesterol, HDL cholesterol, non-HDL cholesterol, and triglyceride-rich lipoprotein cholesterol. Notably, liver fat content decreased by 63.5% in the DR10624 group, compared to only 8.4% in the placebo group, addressing a key comorbidity in severe hypertriglyceridemia. "DR10624 could become a game-changer for patients with severe hypertriglyceridemia by reducing long-term risks of pancreatitis, as well as conditions like MASLD and cardiovascular disease," said lead study author Jianping Li, M.D., Ph.D., of Peking University First Hospital.
The most common side effects were gastrointestinal issues, such as nausea, which are typical with GLP-1 receptor agonists. These were generally mild, but researchers note that gradual dose escalation in future studies may help mitigate symptoms. The study was limited by its small size, short duration, and homogeneous population (all participants were from Mainland China, 89% men), and DR10624 was not directly compared to existing triglyceride-lowering therapies like fibrates or omega-3 fatty acids.
Despite these limitations, the findings are promising for a patient population with few effective options. Current treatments often fail to sufficiently lower triglycerides or address liver fat. DR10624's triple mechanism may offer a multifaceted approach. "Given that DR10624 targets multiple metabolic pathways simultaneously, it could be a strong candidate for combination therapies with other medications," Li noted. Longer-term trials with more diverse participants are needed to confirm safety and efficacy, but these results suggest a potential new standard of care for severe hypertriglyceridemia.
