Key Points:
- DR10624 is a first-in-class triple agonist of the FGF21, glucagon, and GLP-1 receptors, designed to improve metabolic parameters in patients with severe hypertriglyceridemia.
- In a randomized, placebo-controlled Phase 2 trial of 79 adults with severe hypertriglyceridemia (baseline triglycerides 500–2000 mg/dL), weekly subcutaneous DR10624 significantly reduced triglycerides by over 60% while also improving lipoprotein profiles and lowering liver fat after 12 weeks.
- These findings suggest DR10624 may be a promising treatment for patients with severe hypertriglyceridemia, who face limited therapeutic options and high risks of cardiovascular, hepatic, and pancreatic complications.
DR10624 is a novel investigational agent that activates three metabolic receptors – FGF21, glucagon, and GLP-1 – simultaneously. This first-in-class triple agonist was designed to address severe hypertriglyceridemia, a lipid disorder that is challenging to manage with existing therapies. While prior agents have shown modest triglyceride (triglyceride) reductions, they often fail to address the broader metabolic complications of severe hypertriglyceridemia, including hepatic steatosis and elevated atherogenic lipoproteins.
On November 8th, 2025, the results of “DR10624 in Patients with Severe Hypertriglyceridemia: Primary Results for a Randomized Phase 2 Trial” (NCT06555640) were presented at the American Heart Association Scientific Sessions in New Orleans, LA. The purpose of this trial was to determine the safety and efficacy of DR10624 in patients with very high triglyceride levels who are at increased risk for pancreatitis, cardiovascular disease, and metabolic-associated liver disease.
This phase 2 trial randomized 79 adults with fasting triglyceride levels between 500–2000 mg/dL in a 3:1 ratio to receive weekly subcutaneous DR10624 injections at one of three doses (2.5 mg, 25 mg, or 50 mg) or placebo. At baseline, the mean age of participants was 46 years, 89% were male, and all self-identified as Asian (97.5% Han Chinese); approximately 30% of participants were taking background triglyceride-lowering therapy.
At Week 12, DR10624 led to a median triglyceride reduction of 74.5% in the 12.5 mg group, 66.2% in the 25 mg group, and 68.9% in the 50 mg titration group, compared with 8.0% in the placebo group. A significantly higher proportion of DR10624-treated patients achieved triglyceride <500 mg/dL (89.5% vs. 25.0%) and ≥50% triglyceride reductions from baseline (78.5% vs. 5.0%) compared with placebo. DR10624 also improved total cholesterol, HDL-C, non-HDL-C, and triglyceride-rich lipoprotein cholesterol, and was associated with a 63.5% reduction in liver fat, compared with only 8.4% in the placebo group. The most common adverse events were gastrointestinal, such as nausea and abdominal discomfort, which are consistent with the known effects of GLP-1 receptor agonists. The long-term safety and therapeutic durability of DR10624, its effects on clinical outcomes, and its relative efficacy compared with other triglyceride-lowering therapies remain unknown.
Dr. Jianping Li, M.D., Ph.D., a professor and chief in the Institute of Cardiology Disease at Peking University First Hospital in China, concluded: “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. Severe hypertriglyceridemia is often difficult to manage with existing treatments, so access to more treatment choices is crucial for improving patient outcomes as well as quality of life.”
