New research supported by Diabetes Australia has confirmed that a person’s genes can influence how well widely used diabetes medicines such as Mounjaro and Ozempic work.

The discovery could pave the way for more personalised prescribing in the future, with treatments tailored to a person’s genetic profile to improve outcomes.

The findings come from an international team including researchers at Adelaide University and were published in the international journal Genome Medicine.

The research was led by South Australian endocrinologist and clinician researcher Dr Mahesh Umapathysivam (Adelaide University), Dr Alraldi (ETH Zurich), Professor Gloyn (Stanford University) and Prof Stoffel (ETH Zurich), and was supported in Adelaide by funding from the Diabetes Australia Research Program in 2024.

Dr Umapathysivam said the team investigated how genetic differences affect responses to medicines known as GLP-1 receptor agonists, a class of drugs that help lower blood glucose levels and can also assist with weight loss.

“Our studies suggest that a person’s genetic profile may influence how well these medicines slow the emptying of the stomach after eating,” Dr Umapathysivam said.

“This process is important because slower stomach emptying contributes to the medicines’ effect on blood glucose levels.”

The research studied the effect of genetic variants which alter the activity of a protein called PAM. Approximately 10% of the population carry a loss-of-function variant in the PAM gene and have lower PAM activity and higher levels of GLP-1 after meals, but without the expected improvement in the body’s ability to lower blood glucose after a meal, something known as the “incretin” response.

“As a result, these individuals showed a reduced response to GLP-1 receptor agonist medicines,” Dr Umapathysivam said.

“Our findings suggest that people who carry these variants may have a form of GLP-1 resistance, meaning the medicines may not work as effectively for them.”

The team also observed similar patterns in mouse studies, strengthening the evidence that genetic differences can influence how patients respond to this class of medicines.

The discovery could help guide future precision medicine approaches, allowing doctors to better predict who is likely to benefit from these treatments and who may need alternative therapies.

Adelaide’s Laverne Naicker, who was diagnosed with type 2 diabetes about 20 years ago, said she thought it was a shame when Ozempic didn’t work for her.

“I was pretty disappointed,” Laverne said. “It was a big deal. Ozempic seemed to work like a miracle for other people, so why not me?

“For every medication there are side effects. For me, I experienced burping, abdominal discomfort like pinching, and terrible headaches.

“There was no flip side. Ozempic didn’t help with my diabetes. This research is awesome because it has the potential for people like me not to waste time, hope, and feeling unwell if the medication isn’t going to work.”

Laverne has since started insulin to help manage her glucose levels.

Diabetes Australia’s Group CEO Justine Cain said the results highlighted the importance of sustained investment in diabetes research.

“Diabetes Australia is proud to have supported this groundbreaking project,” Ms Cain said.

“Research is the key to changing the future of diabetes.

“Innovative studies like this show how Australian researchers are helping lead the world in understanding diabetes, how to prevent it, and how to improve treatment for people living with the condition.”

Diabetes Australia Group Executive, Health, Economics & Research, Amber Willink, said Dr Umapathysivam’s team’s research supports treatments being used where they will have the greatest benefit.

“Personalised medicine is not a future concept. It’s emerging now. This research shows how genetic insights can help ensure the right treatment reaches the right person at the right time.”

Researchers from the University of Oxford, University of Dundee, University of Copenhagen, University of British Columbia, Newcastle University, University of Bath and University of Exeter also contributed to the work. 

Established almost 40 years ago, the Diabetes Australia Research Program supports outstanding research across prevention, treatment and the search for a cure for all types of diabetes.

The program also helps develop the next generation of diabetes researchers and relies on the generosity of donors to continue supporting world-class research in Australia.

More information about the Diabetes Australia Research Program and how to support its work is available at the Diabetes Australia website. Find out more about how to support us.