Weight Loss Drug HU6 Shows Promise in MASH With Muscle-Sparing Benefits

HU6, an investigational fat-targeted therapy, significantly reduced liver fat in patients with metabolic dysfunction–associated steatohepatitis (MASH) while preserving skeletal muscle mass, according to topline phase 2 results announced by Rivus Pharmaceuticals.¹

In the 6-month M-ACCEL trial (NCT05979779), HU6 achieved statistically significant liver fat reductions across all 3 tested doses compared with placebo (P < .01), meeting its primary endpoint, according to the press release. More than 30% liver fat reduction—a clinically meaningful marker of MASH improvement—was achieved by a statistically significant proportion of patients in each group.

Liver Fat Reduction Without Muscle Loss

MASH is a progressive liver disease that affects about 15 million US adults and is projected to impact more than 23 million adults by 2050.² Caused by a buildup of excess fat in the liver, MASH is often seen in patients with cardiometabolic conditions like obesity or type 2 diabetes, and increases the risk of cardiovascular disease and liver cancer.³ Treatment strategies aim to reduce liver fat, control metabolic dysfunction, and ideally preserve lean muscle mass during weight loss.¹

HU6 appeared to meet these goals, according to Rivus Pharmaceuticals. As a controlled metabolic accelerator, the oral, once-daily small molecule works by increasing resting metabolic rate, helping the body burn fat without requiring behavioral intervention or leading to muscle degradation.

In the M-ACCEL trial, HU6-induced weight loss was exclusively attributed to fat loss, with no statistically significant loss in lean muscle. Approximately three-quarters of the fat loss observed with HU6 was from visceral fat, the type most closely tied to cardiometabolic disease. According to Rivus, this visceral fat-selective loss represents a therapeutic edge, especially in MASH, where reducing intra-abdominal fat is critical for liver health and inflammation control.

“Given the favorable tolerability profile of HU6, the M-ACCEL study reinforces the potential of this investigational treatment to be a promising approach for the long-term management of MASH,” said Mazen Noureddin, MD, professor of medicine at Houston Methodist Hospital and co-chairman of the board of the Summit and Pinnacle Clinical Research Networks.

Full Results to Be Presented

The M-ACCEL trial was conducted at 22 US clinical sites, with more than 200 adults randomized to placebo or HU6 at doses of 150 mg, 300 mg, or 450 mg for 26 weeks. While the trial was not powered to evaluate secondary endpoints, HU6 also demonstrated favorable trends in body weight, hemoglobin A1c (HbA1c), and blood pressure. These improvements were consistent across the dose groups and observed in both patients with and without diabetes—nearly two-thirds of participants had type 2 diabetes at baseline.

“The topline results from M-ACCEL, the longest study of HU6 to date, indicate that HU6 has a competitive efficacy and safety profile for the treatment of MASH,” David Grainger, PhD, chairman of development at Rivus Pharmaceuticals, said in the press release. “Equally important, these data provide continued confirmation of the potential of HU6, and our pipeline of Controlled Metabolic Accelerators, to deliver entirely fat-specific weight loss with a marked propensity for visceral fat reduction for people with obesity and resulting cardiometabolic disease.”

Full results have yet to be published; Rivus plans to present the findings at an upcoming medical meeting but did not specify when or which meeting.

References

1. Rivus Pharmaceuticals announces positive topline results from phase 2 M-ACCEL trial of HU6 showing significant reductions in liver fat in patients with MASH. June 24, 2025. Accessed June 27, 2025. https://www.rivuspharma.com/wp-content/uploads/2025/06/Rivus_M-ACCEL_topline-results_press-release_final_6.23.pdf
2. Le P, Tatar M, Dasarathy S, et al. Estimated burden of metabolic dysfunction-associated steatotic liver disease in US adults, 2020 to 2050. JAMA Netw Open. 2025;8(1):e2454707. doi:10.1001/jamanetworkopen.2024.54707
3. If your patient has cardiometabolic risk factors, act against the underlying threat of MASH. MASH Awareness. Accessed June 27, 2025. https://www.mashawareness.com/