Weight Loss Pill Ingredient Raises Concerns About Gut Health and Inflammation

As oral weight-loss drugs gain popularity, scientists are increasingly examining not just the active ingredient but also the compounds that enable the medication to be absorbed. A new animal study is raising questions about salcaprozate sodium (SNAC), an ingredient used in oral semaglutide medications.

While pills offer a potentially simpler alternative to injections, they also expose the body to additional compounds. Researchers at Adelaide University report that SNAC, used to enhance the absorption of semaglutide tablets, may have effects beyond simply aiding drug delivery. A 21-day study in animals linked repeated SNAC exposure to changes in the gut microbiome and signs of biological changes extending beyond the digestive tract.

What the Study Found

This study was designed to systematically track the effects of ongoing SNAC exposure on gut microbes, their metabolic products, and related signals. Compared to a control group, researchers observed the following in rats:

• Reduced abundance of beneficial gut bacteria involved in breaking down dietary fiber, specifically in Muribaculaceae (-62%) and Bacteroidaceae (-77%).
• Lower levels of short-chain fatty acids (SCFAs), compounds that support gut health and help control inflammation. Fecal butyrate concentrations decreased by 77% with SNAC and 75% with the combination of SNAC and semaglutide.
• Elevated levels of inflammatory markers in the blood, including tumor necrosis factor-α (TNF-α), which increased by 70%.
• Increased liver weight, potentially indicative of low-grade inflammation.
• A smaller cecum, the part of the intestine responsible for breaking down fiber and producing protective compounds.
• Reduced levels of brain-derived neurotrophic factor (BDNF), a protein associated with cognitive function, decreasing by 85%.

These results suggest SNAC may influence the gut ecosystem and inflammation-related pathways, not just medication absorption.

Why SNAC Is Used in Oral Semaglutide

Semaglutide is the active ingredient in weight loss medications like Wegovy and Ozempic. Injections deliver semaglutide directly into the body. Oral formulations face a challenge because the stomach is designed to break down proteins.

SNAC is included in oral semaglutide to protect the drug from enzymatic degradation in the stomach and facilitate its absorption into the bloodstream. Without SNAC, oral semaglutide would be ineffective, making it a crucial component of the medication’s delivery system.

With the approval of a tablet version of Wegovy in the United States in late 2023, and the anticipated rise in oral semaglutide prescriptions, exposure to SNAC is expected to increase significantly.

Obesity Rates and Medication Use

Obesity is a major global health concern, affecting approximately 890 million adults and 160 million children worldwide – roughly one in eight people. The United States has the highest obesity rate among OECD nations, with 43% of people aged 15+ affected. Australia ranks sixth at 31%, compared to the OECD average of 25%.

Prescriptions for medications like Ozempic and Wegovy have increased sharply in recent years in Australia.

Researchers Call for Further Investigation

Amin Ariaee, the lead author and a PhD candidate at Adelaide University, emphasizes the need to fully understand the biological effects of SNAC as oral obesity treatments become more widespread. “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.”

Senior Research Fellow Dr. Paul Joyce cautions that these are early results from animal models and should be interpreted carefully. “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: Ariaee, A., et al. (2026). Gut microbiota perturbation and systemic inflammation are associated with salcaprozate sodium (SNAC)-enabled oral semaglutide delivery. Journal of Controlled Release, 392, 114711. https://doi.org/10.1016/j.jconrel.2026.114711