Hoth Therapeutics, Inc. has announced significant preclinical findings that indicate its glial cell-derived neurotrophic factor (GDNF), co-developed with the United States Veterans Administration, outperforms semaglutide in critical health metrics related to obesity and metabolic disorders. The results, released on February 10, 2026, highlight GDNF’s advantages over semaglutide, the active ingredient in the popular weight-loss drugs Wegovy and Ozempic, particularly in areas such as weight stabilization, glucose tolerance, and liver health.
In a study conducted at the Srinivasan Lab, GDNF demonstrated superior efficacy compared to semaglutide across several key measures. The research utilized CF-1 mice to model human obesity over a 12-week period, administering GDNF at escalating doses, while semaglutide was given at a consistent dose. The findings suggest that GDNF could address some of the limitations associated with current GLP-1 agonists, such as gastrointestinal side effects and muscle loss.
Key Findings from the Study
The study’s results revealed GDNF’s potential to significantly impact weight management and metabolic health. Notably, in female mice following a high-fat Western diet, GDNF reduced weight gain by an impressive 10-15%, leading to stabilization of weight during the latter weeks of treatment. In contrast, semaglutide did not produce significant weight management effects in the same model. Researchers indicated that with higher doses or prolonged treatment duration, GDNF’s benefits could be further enhanced, suggesting promising avenues for sustained weight loss.
In terms of glucose metabolism, GDNF fully normalized fasting glucose levels and improved responses to glucose challenges, outperforming semaglutide in female mice. Similar baseline improvements were noted in male mice, indicating the broader metabolic benefits of GDNF.
The study also emphasized GDNF’s impact on liver and adipose tissue health. GDNF led to a reduction in liver weight by 20-30% and effectively prevented the accumulation of adipose tissue in female models, surpassing the effects seen with semaglutide. These results suggest that GDNF could play a transformative role in addressing fatty liver disease, a common complication associated with obesity.
Future Directions and Company Outlook
Robb Knie, CEO of Hoth Therapeutics, described the study results as a “monumental step forward” in the fight against obesity. He noted that GDNF’s performance not only matches but exceeds that of semaglutide in critical areas, paving the way for safer and more effective treatment options. Hoth plans to accelerate GDNF towards Investigational New Drug (IND)-enabling studies, targeting clinical trials for 2027.
The GDNF program is part of a broader pipeline at Hoth Therapeutics, which includes HT-001, currently in Phase 2 trials for cancer-related skin toxicities, HT-KIT, which has received Orphan Drug Designation for mast cell cancers, and HT-ALZ, aimed at treating Alzheimer’s disease.
Hoth Therapeutics remains committed to advancing innovative therapies that address unmet medical needs, with a patient-centric approach emphasizing collaboration with scientists, clinicians, and key opinion leaders. The results from this study could potentially reshape treatment paradigms in the multi-billion dollar obesity market, which currently affects over 1 billion individuals worldwide.
For more information about Hoth Therapeutics and its ongoing research, visit their website at https://ir.hoththerapeutics.com/.
