Oral versions of popular weight-loss medications work a little differently than the injectable forms many people recognize. Because the active drug would normally break down in the stomach, the tablet includes an added ingredient that helps it survive digestion and enter the bloodstream.
A new study examined that ingredient.
Researchers at Adelaide University studied salcaprozate sodium, or SNAC, the additive that allows semaglutide to be taken as a pill. In a 21-day mouse experiment, they looked at how repeated exposure to SNAC alone affected the gut and other biological markers.
The findings, published in the Journal of Controlled Release, showed shifts in gut bacteria, lower levels of certain short-chain fatty acids that help maintain the gut lining and higher levels of inflammatory markers in the blood. The researchers also observed changes in liver weight and lower levels of a brain-derived protein that has been linked in other research to cognitive impairment.
Importantly, this was an animal study. It did not test full oral semaglutide tablets in people, and it did not measure real-world health outcomes.
“Obesity is a complex, chronic disease with serious health consequences. These medicines are highly effective and are helping many people,” said lead author Amin Ariaee, a PhD candidate at Adelaide University.
He said that as oral versions become more widely used, it is important to understand “what repeated, long-term exposure to all ingredients in the pill means for the body — not just the active drug.”
Senior Research Fellow Dr. Paul Joyce emphasized caution in interpreting the results.
“Importantly, our findings do not prove that SNAC causes harm in humans,” Joyce said. “However, they do show that the ingredient enabling these tablets to work may have adverse biological effects beyond drug absorption.”
The researchers say more work is needed to determine whether similar changes occur in humans and whether those changes translate into meaningful health effects.
It is also worth noting that injectable forms of semaglutide do not contain SNAC.
This study was supported by The Hospital Research Foundation in Australia.