A NOVEL controlled metabolic accelerator, HU6, significantly reduces body weight and fat mass in patients with obesity-related heart failure with preserved ejection fraction (HFpEF), without affecting muscle mass, according to results from the HuMAIN-HFpEF randomised clinical trial.
The HuMAIN-HFpEF trial, a multicentre, randomised, double-blind, placebo-controlled study, evaluated the efficacy and safety of HU6 in 66 patients with chronic, stable obesity-related HFpEF over 19 weeks. Participants, with a mean age of 64.5 years and average BMI of 39.4 kg/m², were randomised to receive HU6 (starting at 150 mg/day, potentially escalating to 450 mg/day) or placebo.
HU6 treatment resulted in a statistically significant reduction in body weight compared to placebo (between-group difference: -2.86 kg; 95% CI, -4.68 to -1.04 kg; P=0.003). Importantly, the weight loss was primarily driven by reductions in total fat mass (-2.96 kg; P<0.001) and visceral fat (-1.3%; P=0.003), with no significant loss of muscle mass. However, the study did not demonstrate significant improvements in exercise capacity, as measured by peak oxygen uptake (VO₂), or other secondary endpoints including 6-minute walk distance, quality of life measures, and biomarkers of heart failure.
While the weight loss achieved was modest compared to GLP-1 receptor agonists, the preservation of lean mass is particularly relevant for older HFpEF patients at risk of sarcopenia and frailty. The safety profile was generally favourable, with serious adverse events deemed unrelated to treatment.
These findings suggest that HU6, by promoting fat-specific weight loss while preserving muscle mass, could potentially offer a novel therapeutic approach for obesity-related HFpEF. However, larger, longer-duration trials are needed to determine whether HU6 can improve functional status, quality of life, and clinical outcomes in this patient population. Future research should also compare HU6 to established weight loss therapies and explore its effects in diverse patient subgroups.
Reference
Pandey A et al. Novel controlled metabolic accelerator for obesity-related HFpEF: the HuMAIN-HFpEF randomized clinical trial. JAMA Cardiol. 2025;DOI:10.1001/jamacardio.2025.0103.
