Berkeley Scientists Find Weight Loss Drug That Keeps Muscle

Scientists at UC Berkeley have identified a promising new treatment for obesity and diabetes that could sidestep some of the biggest concerns with today's popular weight loss medications.

The compound, called TOFA, works differently than drugs like Ozempic and Wegovy. Instead of reducing appetite, it cranks up the body's metabolism to burn more energy naturally.

In mouse studies published in Science Advances, TOFA helped obese mice lose weight from fat without losing lean muscle mass. The mice also showed better blood sugar control and improved liver health.

"Body weight responds to two levers: taking in fewer calories, or spending more energy," said Anders Näär, a UC Berkeley professor who led the research. "GLP-1s work almost entirely on the first, so we went after the second."

TOFA was first discovered in the 1970s but never made it to market. Previous similar compounds raised triglyceride levels, creating heart health risks. The Berkeley team found that TOFA works through a dual mechanism that both blocks fat production and activates genes that help cells burn fat for energy.

The result? Cells burned up to 18% more energy with no change in physical activity or body temperature. Unlike other compounds in its class, TOFA didn't raise dangerous triglyceride levels.

When researchers combined TOFA with existing GLP-1 medications, the results improved even more. Mice showed greater improvements in weight, blood sugar control and triglyceride levels than with either treatment alone.

The Bright Side

This discovery could offer new options for people who struggle with GLP-1 side effects like nausea or muscle loss. The dual approach of blocking fat production while boosting energy expenditure appears to create a coordinated metabolic response that handles excess fat and glucose more effectively.

The muscle preservation is especially important. Many people taking GLP-1s experience muscle loss, which can lead to frailty and other long-term problems. TOFA's ability to burn fat while maintaining lean muscle could address this significant concern.

The researchers have founded a company called ReRx Therapeutics to advance this work toward human trials. They emphasize that TOFA has only been tested in animals so far, and human safety and effectiveness still need to be proven.

Still, the findings offer hope for millions of people managing obesity, diabetes and fatty liver disease. A treatment that works with the body's natural metabolism rather than against appetite could provide a gentler, more sustainable path to better health.