A recent clinical trial of HU6, a novel metabolic accelerator, has shown promising results in reducing fat-specific body weight in individuals suffering from obesity-related heart failure with preserved ejection fraction (HFpEF). While the study demonstrated significant reductions in fat mass, it did not show improvements in exercise capacity or overall physical performance.
The HuMAIN-HFpEF trial, a randomized controlled study involving 66 participants, aimed to evaluate the efficacy of HU6 in improving body composition and exercise capacity. Participants were administered oral doses of HU6 for 19 weeks, starting at 150 mg per day, with potential increases up to 450 mg based on safety and tolerance levels.
Although HU6 produced notable reductions in fat mass and visceral adiposity, it was not as effective as semaglutide, another weight-loss agent, in terms of overall weight loss. However, unlike semaglutide, which reduces both fat and lean muscle mass, HU6 primarily targeted fat loss while preserving lean body mass. This is particularly significant in older individuals with HFpEF, where the preservation of muscle mass is crucial to avoid the risks of sarcopenia and frailty.
Dr. Ambarish Pandey and his team at the University of Texas Southwestern Medical Center led the study. They emphasized that preserving lean mass during weight loss is vital, as a reduction in muscle mass could worsen outcomes for patients, particularly in those already struggling with mobility and physical functioning.
In previous Phase 2 trials, HU6 was shown to induce fat-specific weight loss and preserve lean muscle mass in patients with fatty liver disease. The HuMAIN-HFpEF trial aimed to extend these findings to obesity-related HFpEF, assessing both body composition changes and functional outcomes, including peak oxygen consumption (VO2), exercise capacity, and overall quality of life.
Participants, averaging 64.5 years of age, were enrolled to undergo regular body composition assessments and cardiopulmonary exercise tests. The primary endpoint of the study was the change in body weight from baseline to Day 134, while secondary outcomes focused on improvements in peak VO2 and overall cardiovascular fitness.
After 19 weeks, participants who received HU6 experienced a significant reduction in total body weight (–2.86 kg), with a corresponding decrease in body fat percentage (–2.72%) compared to those who received a placebo. Additionally, the HU6 group saw a 2.96 kg reduction in fat mass, a 1.77% decrease in fat percentage, and a 1.3% reduction in visceral fat. However, there was no significant change in lean mass between the HU6 and placebo groups.
Despite these promising body composition changes, HU6 did not improve exercise capacity, as there were no significant differences observed in peak VO2, exercise time, 6-minute walk distance, or quality of life metrics, including the Kansas City Cardiomyopathy Questionnaire (KCCQ). Furthermore, HU6 showed no effect on biomarkers such as NT-pro-BNP, troponin, hs-CRP levels, or glycemic and lipid parameters.
The trial also reported a few adverse events. Four participants treated with HU6 experienced serious adverse events, compared to one in the placebo group. However, none of these events were deemed related to the treatment.
The findings from this trial suggest that HU6 has potential as a targeted therapy for reducing fat in patients with obesity-related HFpEF, without compromising lean muscle mass. However, the lack of improvements in functional outcomes calls for further investigation. Dr. Pandey and his colleagues recommend additional long-term studies with larger patient populations to better assess the full clinical impact of HU6 on functional outcomes, cardiac health, and overall quality of life.
“Future research with extended treatment periods and larger sample sizes is essential to evaluate HU6’s potential in improving patient functionality, cardiac function, and blood pressure,” concluded the study authors.
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