Hoth Therapeutics's GDNF Treatment Shows Superior Efficacy Over Wegovy, Ozempic In Preclinical Trial

The company announced positive preclinical results from a study evaluating GDNF as a potential treatment for obesity and metabolic-associated steatotic liver disease.

• GDNF outperformed semaglutide, the active ingredient in Wegovy and Ozempic, across several key measures, Hoth said.
• The 12-week study showed that female mice on a high-fat diet experienced a 10% to 15% reduction in weight gain with GDNF, whereas semaglutide showed no meaningful effect.
• The company said GDNF reduced liver weight by 20% to 30% and prevented fat buildup, highlighting its potential to address fatty liver disease.

Hoth Therapeutics (HOTH), on Tuesday, announced preclinical results from a Veterans Administration-backed study evaluating glial cell-derived neurotrophic factor (GDNF) as a potential treatment for obesity and metabolic-associated steatotic liver disease (MASLD).

The company stated that in a head-to-head comparison, GDNF outperformed semaglutide, the active ingredient in weight-loss drugs such as Wegovy and Ozempic, across several key measures, including weight control, glucose tolerance, liver weight reduction, and adipose tissue control.

HOTH shares were up over 5% in pre-market trading but reversed gains after the opening bell, trading 6% lower.

What Did The 12-Week Study Show?

During the 12-week study, female mice on a high-fat diet experienced a 10% to 15% reduction in weight gain with GDNF, eventually entering a stabilization phase, whereas semaglutide showed no meaningful effect. Researchers noted that higher doses or longer durations could amplify GDNF’s effects.

GDNF also normalized fasting glucose levels and improved responses to glucose challenges. Additionally, the therapy reduced liver weight by 20% to 30% and prevented fat buildup, highlighting its potential to address fatty liver disease, a common issue with obesity.

“These results are a monumental step forward for Hoth and the fight against obesity. GDNF not only matched but exceeded semaglutide in critical areas, opening doors to a new era of safer, more effective therapies,” said Robb Knie, CEO of Hoth Therapeutics.

What’s Next?

Hoth plans additional studies on liver pathology, lipid content, and gene and protein expression to better understand GDNF’s mechanism, with clinical trials targeted for 2027.

Weight-loss drugs have become a central focus for the pharmaceutical industry, driving revenue growth for leaders like Eli Lilly and Novo Nordisk as other companies race to enter the booming market.

The segment has been under regulatory spotlight in the aftermath of Hims & Hers launching a compounded version of Wegovy last week, which the company has since withdrawn following legal notices from NOVO and the U.S. Food and Drug Administration.  

How Did Stocktwits Users React?

Retail sentiment turned ‘bullish’ from ‘neutral’ a day earlier, accompanied by ‘high’ message volumes.

One user called for patience amid the intraday decline.

HOTH shares are down around 21% so far this year.

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