Old Compound TOFA Boosts Weight Loss Drugs in Mice

Researchers at the University of California, Berkeley report the experimental compound makes cells burn fat for energy.

Updated on Nov. 3, 2026 in Weight Loss

Close view of a clear glass culture plate holding faint amber liquid on a pale lab bench beside pipette tips in soft daylight. — University of California, Berkeley researchers report that the experimental compound TOFA, created in the 1970s, boosted weight loss when combined with semaglutide or tirzepatide in obese mice. AI Illustration. Upload story photo >

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University of California, Berkeley researchers report that TOFA, a manmade compound created in the 1970s, makes cells burn fat for energy. In obese mice, TOFA combined with semaglutide or tirzepatide produced substantially more weight loss than either drug alone.

Why it matters

The findings suggest a way to amplify existing weight-loss drugs while preserving lean tissue, which current treatments often fail to do. TOFA has not yet been tested in humans, and researchers still must rule out excessive heat production and strain on the heart.

In mice, TOFA alone produced 18 per cent weight loss over four weeks with almost all lost weight being fat, while combinations with semaglutide or tirzepatide roughly doubled or tripled the effect of low-dose drugs alone. The results come from animal work, and no human trial data exists yet.

The players

University of California, Berkeley

A public research university in Berkeley, California, whose researchers conducted the study on TOFA.

Naveed Sattar

A professor at the University of Glasgow who commented on the findings and is an expert in metabolic disease.

Alex Miras

A researcher at Ulster University who commented on the findings and studies obesity treatment.

The details

TOFA blocks enzymes involved in making new fat and activates two proteins that switch on genes for burning fat and producing energy. Researchers combined low doses of semaglutide or tirzepatide with TOFA, and the combinations allowed the drugs to work at lower doses than typical obesity treatments.

1970s: TOFA was created as a manmade compound and never developed into a medicine.
Four weeks: Obese mice given TOFA lost about 18 per cent of body weight.
24 days: The combination dosing trial measured weight loss in mice.

Big Picture

Like metformin, a decades-old drug repurposed for metabolic benefit, TOFA was an overlooked compound that researchers revisited for its fat-burning effect. The findings point toward combination approaches that pair fat-burning mechanisms with GLP-1 drugs such as semaglutide and tirzepatide.

For readers managing weight, the research does not yet change treatment options, since TOFA has only been tested in mice. Anyone considering semaglutide or tirzepatide should continue to follow their clinician's guidance until human trials report results.

The takeaway

Combining older lab compounds with current weight-loss drugs may become a useful strategy, but human safety data will decide whether it reaches clinics. Readers should treat the mouse results as early-stage evidence rather than a treatment option.