Hoth Therapeutics’ Experimental GDNF Outperforms Semaglutide, Cuts Liver Weight 20-30%
Hoth Therapeutics’ GDNF candidate attenuated weight gain by 10-15%, reduced liver weight by 20-30% and prevented adipose accumulation in female mice, outperforming semaglutide across glucose tolerance and metabolic metrics. VA-backed preclinical data supports advancing GDNF into IND-enabling studies targeting 2027 clinical trials, offering a differentiated obesity therapy mechanism.
1. Preclinical Head-to-Head Results
In female mice fed a high-fat Western diet, GDNF treatment attenuated weight gain by 10-15%, fully normalized fasting glucose and improved glucose tolerance. It also reduced liver weight by 20-30% and prevented adipose tissue accumulation, outperforming semaglutide on all measured metabolic endpoints.
2. Study Backing and Next Steps
The study was supported by the U.S. Veterans Administration and included both male and female models. Hoth plans IND-enabling studies in 2026 with the goal of initiating clinical trials in 2027, while additional analyses on liver pathology, lipid content and gene expression are underway.
3. Pipeline Context
GDNF’s obesity and MASLD program complements Hoth’s pipeline, which includes HT-001 in Phase 2 for cancer-related skin toxicities, HT-KIT with orphan drug designation for mast cell cancers and HT-ALZ targeting Alzheimer’s disease.