Blockbuster weight-loss drugs are transforming the way we treat obesity. But while costly injectable versions remain out of reach for many, newly approved tablet forms are expected to significantly boost access and demand.
A new study from Adelaide University is turning a spotlight on those tablet versions, finding that the absorption-enhancing ingredient salcaprozate sodium (SNAC) may have measurable adverse biological effects for the gut and beyond.
It is the first in vivo study to systematically evaluate the effects of repeated SNAC exposure on gut microbiota composition, function, and metabolic outcomes. In an animal model extending 21 days, researchers identified:
- Lower levels of beneficial gut bacteria that help break down dietary fibre
- Reduced short-chain fatty acids which protect the gut lining and help regulate inflammation
- Higher levels of blood inflammatory markers
- An increase in liver weight, which can reflect low-grade inflammation
- A smaller caecum – the part of the intestine where gut bacteria break down fibre and produce protective compounds
- Reduced levels of a brain-derived protein associated with cognitive impairment.
While the study does not directly show that SNAC causes harm, the findings suggest that the absorption enhancer may have biological effects beyond simply helping semaglutide work in pill form.
The role of SNAC
Semaglutide is the active ingredient in weight loss medicines. When injected, it enters the bloodstream directly. In tablet form, it relies on SNAC to protect it from enzymatic degradation in the stomach and enable absorption into the bloodstream. Without SNAC, oral semaglutide would not work.
With the United States approving the Wegovy tablet late last year, and expectations that it will be cheaper and more convenient than injections, long‑term daily exposure to SNAC is likely to increase substantially.
Globally, about 890 million people and 160 children live with obesity, equivalent to one in eight people worldwide. The United States has the highest obesity rate among OECD countries with 43 per cent of people aged 15+ living with the condition; Australia ranks sixth at 31 per cent, above the OECD average of 25 per cent.
In Australia prescriptions for drugs such as Ozempic and Wegovy have risen sharply in recent years.
Greater understanding needed
Lead author and Adelaide University PhD candidate Amin Ariaee says the rapid growth in oral obesity treatments that utilise SNAC makes it critical to understand its full biological impact, in order to mitigate any longer-term adverse health effects.
‘Obesity is a complex, chronic disease with serious health consequences. These medicines are highly effective and are helping many people,’ Ariaee says.
‘But 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.
‘While SNAC enables semaglutide to be taken as a tablet, our study found that it was also associated with shifts in potentially harmful gut bacteria, elevated inflammatory markers and depletion of proteins linked to cognitive impairment. These findings warrant further investigation.’
Early results
Senior Research Fellow Dr Paul Joyce says that as these are early results from animal models – not humans – the findings should be interpreted carefully and highlight an important research gap.
‘Importantly, our findings do not prove that SNAC causes harm in humans,’ Dr Joyce said. ‘However, they do show that the ingredient enabling these tablets to work may have adverse biological effects beyond drug absorption.
‘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.’
