A novel obesity treatment compound called SANA has shown promising results in its first human clinical trial, demonstrating weight loss and improved metabolic markers through a unique mechanism that activates the body's natural heat-generating processes. The phase 1 study, which tested the safety and tolerability of this salicylate derivative, represents a potential breakthrough in addressing one of the world's most challenging health conditions.
Unexpected Discovery Leads to Clinical Development
Scientists originally designed SANA, short for 5-(2-nitroethenyl)salicylic acid, to combat inflammation, a key factor in obesity-related illnesses. However, early experiments revealed an unexpected property: the compound prevented mice from gaining weight even when consuming high-fat diets. Animals already obese shed significant weight within weeks, reducing liver fat and improving insulin sensitivity.
"We conducted tests with UCP1-deficient mice and proved that SANA activates thermogenesis even without this protein and under normal temperature conditions," said William Festuccia, professor at the Biomedical Sciences Institute at the University of São Paulo.
Novel Mechanism Targets Fat Tissue Specifically
Unlike most weight-loss medications, SANA works by activating thermogenesis through a previously unexplored pathway. While normal thermogenesis involves a protein called UCP1 within mitochondria, SANA stimulates calorie burning without UCP1, instead utilizing creatine cycles in adipose tissue.
This distinct mechanism means SANA specifically targets fat tissue, reducing the risk of overheating and cardiovascular stress associated with older thermogenic drugs. The compound increases mitochondrial respiration and enhances the creatine cycle in fat tissue, where creatine cycles between forms while consuming energy and releasing heat.
Encouraging Phase 1 Clinical Results
The rigorous phase 1 clinical trial involved healthy, overweight, and obese volunteers and was conducted in two parts. Researchers evaluated single doses ranging from 200 to 800 mg and multiple doses from 200 to 400 mg daily for 15 days.
Participants tolerated SANA well, experiencing no severe side effects. Most significantly, those taking the highest dose showed improved insulin resistance and weight loss within just two weeks. "The observed effects were significantly stronger than what we've seen with salicylate alone," noted researcher Carlos Escande from the Pasteur Institute in Montevideo, Uruguay.
Potential for Combination Therapy
SANA could become the first in a new class of obesity drugs with potential to complement existing treatments like GLP-1 agonists. Because it uses a novel mechanism, it can potentially combine with drugs like semaglutide to enhance overall weight-loss effectiveness.
"When food intake is reduced, metabolism tends to slow down. Combining a molecule that suppresses appetite with another boosting caloric expenditure could prevent the plateau effect often seen in dieting," explained Marcelo Mori from the Institute of Biology at the State University of Campinas.
Unlike GLP-1 drugs that sometimes cause muscle loss, particularly concerning for elderly users, SANA specifically burns fat without affecting muscle mass. "That's why having alternatives is important," Mori added.
Scientific Foundation and Future Directions
SANA's beneficial effects stem from the nitroalkene chemical group attached to salicylate, which triggers several beneficial pathways related to cellular energy production. Scientists initially explored nitroalkenes using vitamin E structures, finding improvements in inflammation, glucose intolerance, and heart disease during obesity before testing the combination with salicylate.
"We observed weight loss and improved blood sugar levels in obese volunteers who participated in the phase 1 clinical trial," Escande explained. However, he cautioned that "this result isn't conclusive because it was a small group, and the objective was to assess whether the compound is safe and well-tolerated."
Researchers now plan to advance to phase 2 clinical trials focusing on proving SANA's effectiveness in larger human populations. "We intend to start phase 2 of the study later this year, designed specifically to test effectiveness," Escande emphasized.
If successful in larger trials, SANA might represent a significant advancement in obesity treatment, providing a safer, more efficient approach to weight and metabolic health management by harnessing the body's natural heat-generating processes in a targeted manner.
