New Multi-Receptor Medication Shows Promise for Severe Triglyceride Reduction and Liver Health

An 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 findings suggest this first-of-its-kind therapy could address multiple metabolic issues simultaneously in patients who often have limited treatment options.

The Phase 2 clinical trial involved 79 adults with severe hypertriglyceridemia, defined as triglyceride levels between 500-2,000 mg/dL. Participants received either weekly subcutaneous injections of DR10624 at varying doses or a placebo for 12 weeks. The study was conducted across 35 healthcare centers in Mainland China between September 2024 and March 2025.

DR10624 represents a novel approach by activating three different receptors simultaneously: FGF21, glucagon and GLP-1 receptors, all involved in regulating how the body processes fats and sugars. This multi-receptor targeting distinguishes it from existing treatments and may explain its broad metabolic effects.

After 12 weeks of treatment, patients receiving DR10624 showed dramatic reductions in triglyceride levels across all dosage groups. The 12.5 mg dose group experienced a 74.5% reduction, the 25 mg group had a 66.2% reduction, and the 50 mg titration group showed a 68.9% reduction. This compares to only an 8.0% reduction in the placebo group. Importantly, 89.5% of DR10624 patients achieved triglyceride levels below 500 mg/dL, compared to just 25.0% of placebo patients.

The medication's impact extended beyond triglyceride reduction. Patients treated with DR10624 showed a 63.5% reduction in liver fat, a crucial finding since many people with severe hypertriglyceridemia also develop excess liver fat, leading to metabolic dysfunction-associated steatotic liver disease (MASLD). The placebo group showed only an 8.4% reduction in liver fat. Additional improvements were noted in other lipid measures including total cholesterol, high-density lipoprotein cholesterol, non-HDL cholesterol and triglyceride-rich lipoprotein cholesterol.

This development matters because severe hypertriglyceridemia presents significant health risks beyond the elevated lipid levels themselves. High triglycerides combined with unfavorable cholesterol profiles contribute to fatty buildup in artery walls, increasing the risk of heart attack and stroke. Elevated triglycerides also raise the risk of pancreatitis, a serious and potentially life-threatening condition. The concurrent reduction in liver fat addresses another major concern, as MASLD can progress to more severe liver inflammation and damage known as metabolic dysfunction-associated steatohepatitis (MASH).

Current treatment options for severe hypertriglyceridemia include fibrates, concentrated omega-3 fatty acids, and statins, but these often provide insufficient triglyceride lowering and limited effects on liver fat. The lack of effective standard therapies for MASLD further compounds the treatment challenge for patients with both conditions.

Lead study author Jianping Li, M.D., Ph.D., from Peking University First Hospital in China, 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 MASLD and cardiovascular disease." He emphasized that severe hypertriglyceridemia is often difficult to manage with existing treatments, making access to more treatment choices crucial for improving patient outcomes and quality of life.

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 alleviate these symptoms.

The study authors acknowledge several limitations, including the short 12-week duration, small participant size, and exclusive focus on patients in Mainland China. The research also did not directly compare DR10624 against existing triglyceride-lowering medications. Future studies will need to examine longer-term safety and efficacy in more diverse populations. Additional 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.

Researchers plan to explore DR10624's potential in combination therapies with other medications, such as glucose-lowering drugs like SGLT2 inhibitors or DPP-4 inhibitors, which could benefit patients with additional conditions like Type 2 diabetes, obesity, and cardiovascular disease. The multi-pathway approach of DR10624 makes it a strong candidate for such combination strategies aimed at comprehensive metabolic control.