Might Thermogenesis Be Viable for Obesity Treatment?

In drug therapy for obesity, all of the excitement about GLP-1s and now amylin analogs has focused on regulation of eating behaviors. But, in fact, this is just one part of the process for regulating metabolic function and adiposity. Until now, we have seen little success in developing safe and effective medicines that alter the use of energy by our bodies. A new paper in Nature Metabolism gives us a signal that thermogenesis might be a useful mechanism for obesity treatment, stimulating the body to use more of the calories we consume.

Stated simply, thermogenesis is the metabolic process of burning calories to keep a body warm.

SANA is a relatively obscure experimental drug which is a nitro-alkene derivative of salicylate. Both animal and phase one human studies in this new paper suggest that SANA may stimulate thermogenesis in a way that promotes weight loss.

Encouraging Signs

In their new paper, Karina Cal, Alejandro Leyva, and colleagues report data from preclinical studies in mice to show that this drug could both prevent and reverse the effects of diet-induced obesity (DIO). Their results indicate that it works by stimulating creatine-dependent thermogenesis.

They also report the results of a small phase one study in humans with the primary aim of assessing the drug’s safety. But not only did they see good signs for its safety, they also found favorable effects on body weight. In 15 days of treatment, subjects in the higher dose group lost three percent of their starting body weight.

These researchers are enthusiastic about what they found:

“The current study presents compelling preclinical and clinical evidence that SANA is a potent drug for the treatment of DIO, with a primary mechanism of action being the activation of creatine-dependent energy expenditure and thermogenesis in adipose tissue.”

Early, Incomplete Evidence

But we must bear in mind that this is the only peer-reviewed study we can find on this drug. The authors themselves advise caution:

“Although the human results obtained during the phase 1A/B clinical trial supports the notion that SANA may be effective in humans, it is important to take into consideration that the clinical trial was designed with the main objective of determining safety and tolerability, with a limited number of volunteers and clinical determinations. In that sense, the efficacy of SANA in humans needs to be further studied in a phase 2 clinical trial, with longer treatment, increased sample number, and extended measurements to validate its efficacy and mechanism of action. As such, the efficacy results presented here, although promising, are still preliminary and subject to further validation.”

Obesity medicine physician and researcher Caroline Apovian was not involved in this research. But she has studied the concept of thermogenesis in obesity for some time. In sum, she says that this drug may be promising because it points to a new pathway for altering thermogenesis. But we need to be cautious, she says, because thermogenesis has proven to be a tricky thing to alter in the past.

It’s a bit like playing with fire.

Click here for the new study in Nature Metabolism and here for further reporting on it. For more background on thermogenesis in obesity, click here.

Fire, painting by Giuseppe Arcimboldo / WikiArt

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June 19, 2025