Oral weight-loss drugs have been hailed as a medical breakthrough, promising powerful results without injections. But new Australian research suggests a key ingredient in these pills may cause unintended biological consequences.
The study from Adelaide University, published in the Journal of Controlled Release, found a key ingredient in oral weight-loss drugs, salcaprozate sodium (SNAC), could cause biological changes in the gut microbiome and metabolism.
Using mice models over 21 days, researchers found reduced healthy gut bacteria, more inflammation markers, increased liver weight, which is associated with low-grade inflammation, and a smaller caecum—a section of the intestines where bacteria break down fibre to produce protective compounds. Researchers also observed lower levels of brain proteins that help cognitive function.
“We observed reductions in certain gut bacteria that are generally considered beneficial, lower levels of butyrate, which supports gut health and inflammation regulation, and higher levels of circulating inflammatory markers,” said lead author Amin Ariaee, a PhD candidate at the University of Adelaide.
No Evidence of Clinical Harm
The researchers emphasised that their findings do not demonstrate harm to humans.
Ariaee told The Epoch Times the results came from a short-term study in rats, not humans, so conclusions should not be made too early.
“It is important to be clear that our study does not show clinical harm from SNAC,” he said.
Senior Research Fellow Dr Paul Joyce stressed that the outcomes highlight the need to better understand the effects of absorption enhancers as oral weight-loss medications rapidly expand.
“They do show that the ingredient enabling these tablets to work may have adverse biological effects beyond drug absorption,” Joyce said in a media release.
“These medicines are typically taken daily and often for long periods. As their use expands globally, it becomes increasingly important to evaluate all components of these therapies, not just the active compound.”
Why SNAC is Used
Semaglutide, the active ingredient in medications such as Ozempic and Wegovy, is a glucagon-like peptide-1 (GLP-1) receptor agonist that suppresses appetite, slows gastric emptying, and improves insulin regulation, especially in type 2 diabetes.
Semaglutide can be delivered through two methods: injections or tablets (pills).
Injectable forms bypass the digestive system and enter directly into the bloodstream. Tablet forms, however, face a significant challenge: stomach acid can break down semaglutide before it is absorbed.
To circumvent this, oral pills are packaged with SNAC.
“SNAC works locally in the stomach by temporarily increasing the local pH and enhancing permeability across the gastric lining, which allows semaglutide to enter the bloodstream before it is broken down,” Ariaee said.
Without SNAC, oral semaglutide would not be effective.
Rising Popularity in Weight-Loss Medication
Obesity affects one in eight people worldwide, which the World Health Organisation estimates is 890 million adults as of 2022.
In Australia, two-thirds of adults are overweight or living with obesity, ranking as the sixth most prevalent country among OECD nations.
Australian prescriptions for these semaglutide medications have risen sharply in recent years.
A review conducted by Associate Professor Michael Falster from UNSW Sydney found a 10-fold increase in the total sales between May 2020 and April 2025, reaching approximately half a million units each month.
Associate Professor Suong Le, a gastroenterologist at Monash University’s School of Clinical Sciences, says Australia is at a “watershed” moment in obesity management.
She says new medications are transforming the way obesity is viewed, especially against the backdrop of a growing demand for weight loss medications.
“As oral versions become more widely used, we need to understand what repeated, long-term exposure to all ingredients in the pill means for the body, not just the active drug,” Ariaee said.
Future Steps
The findings from the study prompt long-term investigations, especially as oral weight-loss medicines continue to expand globally.
“Before our findings could be translated into clinical practice, more research on the gut impacts of these absorption enhancers would be required,” Ariaee told The Epoch Times.
“Our study certainly highlights the need to better understand how absorption enhancers like SNAC may affect the gut over time.”
He noted that research is underway for oral weight-loss medications that do not use SNAC.
“There are alternatives to peptide-based oral GLP-1 medicines,” he said. “Small molecule GLP-1 drugs such as orforglipron and ECC5004 are in clinical development and do not require absorption enhancers like SNAC.”
Importantly, pharmaceutical medications alone cannot replace lifestyle-based approaches, but rather complement them.
“[For medications] their benefits often reduce once treatment stops, so they are not a replacement for a healthy diet and physical activity,” Ariaee said.
“They are best viewed as part of a broader approach to long-term metabolic health.”