Obesity pill targets fat, keeps muscle

A groundbreaking weight-loss drug that could help people shed kilos without losing muscle is being developed at Waipapa Taumata Rau, University of Auckland.

Unlike existing weight-loss drugs that work by reducing appetite, the new treatment targets fat storage and could help people lose weight without sacrificing the enjoyment of food, says Peter Shepherd, Professor of Cell Signalling in the Department of Molecular Medicine and Pathology at the Faculty of Medical and Health Sciences.

The University researchers received $1.198 million in Health Research Council funding over three years to advance the treatment, which targets the body's fat-storage processes rather than suppressing appetite.

"We've found this pathway inside cells that ultimately affects fat storage, and made a drug that targets that pathway,” Shepherd says.

“We're the first in the world to be developing this type of treatment. Unlike GLP-1 medications such as Wegovy, which reduce appetite and food intake, the treatment aims to prevent fat accumulation.

"Preclinical data suggest it's safe to target this mechanism long term, and we are getting weight loss at least as good as would be expected with Wegovy.”

While Wegovy is typically administered by injection, the new treatment is being developed as an oral pill.

In preclinical studies, the drug has not reduced appetite or food intake, suggesting people may continue to enjoy eating while still losing weight,  Shepherd says.  

Researchers also believe the approach may avoid one of the key drawbacks of other weight-loss medicines.

"Our drug strategy overcomes some of the problems that are associated with Mounjaro and Wegovy, which result in loss of muscle mass," says Dr Chris Hedges, an investigator in the studies.

"Muscle loss is particularly dangerous for older people and is associated with poorer health outcomes as people age,” Hedges says.

“It can lead to frailty, increasing the risk of falls and fractures and reducing the ability to recover strength."

The study will compare the drug to GLP-1 weight-loss medicines in terms of effectiveness and potential advantages. 

Professor Rinki Murphy, an endocrinologist and co-investigator, says the research is exciting because it could open the door to testing new approaches to obesity treatment.

“As obesity is driven by multiple biological pathways, there is real potential to combine medicines that work in different ways to achieve greater weight loss while preserving muscle mass and improving long-term health outcomes,” Murphy says.

Researchers have concluded the laboratory phase of the project and are now moving into preclinical development to prepare the treatment for human clinical trials.

Shepherd and colleagues are seeking investors for a biotechnology company to bring the technology to market.

"The market for weight-loss drugs is currently around US$50 billion a year, and if we could get even a small percentage of that for drugs of our type, it would represent a really large economic opportunity for New Zealand," he says.