New Multi-Receptor Medication Shows Promise in Reducing Triglycerides and Liver Fat

A new investigational medication called DR10624 reduced triglyceride levels by more than 60% in most patients with severe hypertriglyceridemia while also significantly decreasing liver fat, according to preliminary research presented at the American Heart Association's Scientific Sessions 2025. The Phase 2 clinical trial tested whether DR10624 could safely and effectively lower very high levels of triglycerides in people with severe hypertriglyceridemia (500-2,000 mg/dL), who face increased risks of cardiovascular disease and pancreatitis.

DR10624 represents a first-of-its-kind approach by simultaneously activating three different receptors linked to triglyceride metabolism: FGF21, glucagon and GLP-1 receptors. This multi-receptor targeting distinguishes it from current treatments like fibrates, concentrated omega-3 fatty acids, or statins, which don't always provide sufficient triglyceride lowering and may have limited effects on liver fat. The study's lead author, Jianping Li, M.D., Ph.D., noted that DR10624 could become a game-changer for patients with severe hypertriglyceridemia by reducing long-term risks of pancreatitis, as well as conditions like metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular disease.

The 12-week trial involved 79 adults with severe hypertriglyceridemia randomly assigned to receive either weekly subcutaneous injections of DR10624 at one of three doses (12.5 mg, 25 mg or 50 mg titration) or a placebo. Results showed dramatic improvements across all treatment groups: patients receiving the 12.5 mg dose achieved a 74.5% reduction in triglycerides, the 25 mg group had a 66.2% reduction, and the 50 mg titration group showed a 68.9% reduction, compared to only 8.0% reduction in the placebo group. Importantly, 89.5% of DR10624 patients achieved triglyceride levels below 500 mg/dL, compared to only 25.0% of placebo patients.

Beyond triglyceride reduction, patients treated with DR10624 experienced a 63.5% reduction in liver fat, compared to only 8.4% reduction in the placebo group. This finding is particularly significant because many people with severe hypertriglyceridemia also have excess fat in the liver, which can progress to more serious conditions like metabolic dysfunction-associated steatohepatitis (MASH). Currently, there are no standard therapeutic treatments for MASLD and only one FDA-approved therapy for MASH, making this additional benefit particularly valuable.

The medication also improved other important lipid measures, including total cholesterol, high-density lipoprotein cholesterol, non-HDL cholesterol and triglyceride-rich lipoprotein cholesterol. The most common side effects were gastrointestinal issues such as nausea or stomach upset, which are typical with medications targeting GLP-1 receptors. Researchers suggested that gradually increasing the dose over several weeks in future studies might help ease these symptoms.

Study limitations included the short 12-week duration, small sample size, and exclusive participation of individuals from Mainland China, meaning findings cannot yet be generalized to broader populations. Additionally, DR10624 was not directly compared to other approved triglyceride-lowering medications, so its relative effectiveness and safety compared to existing treatments remains unknown. The researchers emphasized that longer-term trials with more diverse participants are needed to fully assess the medication's safety and efficacy profile.

Given DR10624's mechanism of targeting multiple metabolic pathways simultaneously, researchers suggested it could be a strong candidate for combination therapies with other medications, such as glucose-lowering drugs like SGLT2 inhibitors or DPP-4 inhibitors, potentially improving overall metabolic control in patients with conditions like Type 2 diabetes, obesity and cardiovascular disease. More information about the study can be found in the American Heart Association Scientific Sessions 2025 Online Program Planner at https://professional.heart.org/en/meetings/scientific-sessions.