Hoth Therapeutics’ HT-VA GDNF shows superior efficacy in obesity

Hoth Therapeutics (HOTH) announced “compelling” preclinical data from its VA-backed study on glial cell-derived neurotrophic factor, or GDNF, as a novel treatment for obesity and metabolic-associated steatotic liver disease, or MASLD. In a head-to-head comparison, GDNF demonstrated superior efficacy over semaglutide – the active ingredient in Wegovy and Ozempic – in key metrics, including weight stabilization, glucose tolerance, liver weight reduction, and adipose tissue control-particularly in female models. This breakthrough positions GDNF as a potential gamechanger in the $200B obesity market, offering a differentiated mechanism that could address limitations of current GLP-1 agonists like gastrointestinal side effects and muscle loss. In female mice on a high-fat Western diet, GDNF attenuated weight gain by 10-15%, leading to a plateau in the final weeks of treatment-unlike semaglutide, which showed no significant impact. Researchers noted that higher doses or longer durations could amplify GDNF’s effects. GDNF fully normalized fasting glucose and improved overall response to glucose challenges, outperforming semaglutide in females. Baseline improvements were also seen in males, indicating broad metabolic benefits. GDNF reduced liver weight by 20-30% and prevented adipose tissue accumulation in females, surpassing semaglutide’s effects.