Why Scientists Are Urging Caution About a Common Ingredient in Semaglutide and Ozempic

A new animal study raises important questions about a little-known ingredient used in oral weight-loss medications.

A pill can feel simpler than a shot, but it also changes what else your body is exposed to.

Researchers at Adelaide University report that salcaprozate sodium (SNAC), the ingredient used to help semaglutide tablets get absorbed, may do more than just usher the drug into the bloodstream. In a 21-day animal study, repeated SNAC exposure was linked to shifts in the gut microbiome and signs of broader biological changes that reached beyond the digestive tract.

This was the first in vivo study designed to systematically track how ongoing SNAC exposure affects gut microbes, what those microbes produce, and related metabolic signals. Compared with controls, the researchers observed:

• Fewer beneficial gut bacteria involved in breaking down dietary fiber
• Lower levels of short-chain fatty acids, compounds that help support the gut lining and play a role in inflammation control
• Higher levels of inflammatory markers in the blood
• Increased liver weight, which can be consistent with low-grade inflammation
• A smaller cecum – the part of the intestine where gut bacteria break down fiber and produce protective compounds
• Reduced levels of a brain-derived protein associated with cognitive impairment

Taken together, the results suggest SNAC may influence the gut ecosystem and inflammation-related pathways, not just medication absorption. The study does not show that SNAC causes harm, and it does not establish what these signals would mean in people, but it does raise a practical question: what happens when an ingredient designed for delivery becomes part of a daily routine for years?

Why SNAC Is Used in Oral Semaglutide

Semaglutide is the active ingredient in weight loss medicines. Injections deliver it directly into the body. Tablets face a tougher environment because the stomach is built to break proteins down.

In oral semaglutide, SNAC is included to protect the drug from enzymatic degradation in the stomach and help it cross into the bloodstream. Without SNAC, oral semaglutide would not work. That makes SNAC less like an inactive filler and more like a key piece of the medication’s delivery system.

The United States approved a tablet version of Wegovy late last year. Because pills are expected to be less expensive and more convenient than injections, daily and long term exposure to SNAC is likely to rise significantly.

Obesity remains a major global health issue. Around 890 million adults and 160 million children worldwide are living with obesity, which equals roughly one in eight people. Among OECD nations, the United States has the highest obesity rate, with 43% of people aged 15+ affected. Australia ranks sixth at 31%, compared with the OECD average of 25%.

In Australia, prescriptions for medications such as Ozempic and Wegovy have increased sharply in recent years.

Researchers Call for Further Investigation

Lead author and Adelaide University PhD candidate Amin Ariaee says the rapid expansion of oral obesity treatments that utilize SNAC makes it essential to fully understand its biological effects to reduce any potential long term health risks.

“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.”

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 says.

“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.”

Reference: “Gut microbiota perturbation and systemic inflammation are associated with salcaprozate sodium (SNAC)-enabled oral semaglutide delivery” by Amin Ariaee, Karim Noueihad, Alex Hunter, Anthony Wignall, Hannah R. Wardill, Maya Davies, Clive A. Prestidge and Paul Joyce, 9 February 2026, Journal of Controlled Release.
DOI: 10.1016/j.jconrel.2026.114711

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