The convenience of taking weight loss medication as a pill, rather than by injection, may approach with previously unconsidered effects on gut health, according to fresh research from Adelaide University in Australia. A study published this week reveals that salcaprozate sodium (SNAC), the ingredient that allows oral semaglutide – the active ingredient in drugs like Wegovy and Ozempic – to be absorbed, is linked to changes in gut bacteria, increased inflammation and even a reduction in a protein associated with brain health in animal models. Whereas the findings don’t demonstrate harm to humans, they raise important questions about the long-term consequences of widespread SNAC exposure as oral versions of these medications become increasingly popular.
The study, described as the first in vivo investigation into the effects of repeated SNAC exposure, observed notable shifts in the gut microbiome of rats over a 21-day period. Researchers found a decline in beneficial gut bacteria responsible for breaking down dietary fiber, alongside lower levels of short-chain fatty acids – crucial compounds that support gut lining health and help regulate inflammation. These changes were accompanied by increased levels of inflammatory markers in the blood and a larger liver weight, potentially indicating low-grade inflammation. The research, published in Gut Microbiota Perturbation and Systemic Inflammation, also noted a smaller cecum, the part of the intestine where fiber is broken down, and reduced levels of brain-derived neurotrophic factor (BDNF), a protein linked to cognitive function.
How SNAC Enables Oral Semaglutide
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is highly effective in treating obesity and type 2 diabetes. When administered via injection, the drug is readily absorbed into the bloodstream. However, semaglutide is vulnerable to breakdown by stomach enzymes, rendering it ineffective if taken orally without assistance. SNAC acts as an “absorption enhancer,” protecting the drug from digestion and facilitating its passage into the bloodstream. Without SNAC, oral semaglutide would not work, according to researchers.
The U.S. Food and Drug Administration approved a tablet version of Wegovy late last year, offering a more convenient alternative to weekly injections. This shift is expected to increase exposure to SNAC as more individuals opt for the oral formulation.
Global Obesity Rates and Rising Medication Employ
The need for effective obesity treatments is pressing. Around 890 million adults and 160 million children worldwide are living with obesity, representing roughly one in eight people globally. Among countries in the Organisation for Economic Co-operation and Development (OECD), the United States has the highest obesity rate, affecting 43% of people age 15 and older. Australia ranks sixth at 31%, exceeding the OECD average of 25%.
Prescriptions for medications like Ozempic and Wegovy have been increasing rapidly in Australia, mirroring a global trend. This increased demand underscores the importance of understanding the potential effects of all components within these medications, not just the active drug.
The Need for Further Research
Amin Ariaee, a PhD candidate at Adelaide University and lead author of the study, emphasized the importance of understanding the long-term 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 said. “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.”
The researchers found that SNAC was associated with shifts in gut bacteria, elevated inflammatory markers, and depletion of proteins linked to cognitive impairment. “These findings warrant further investigation,” Ariaee added.
Senior Research Fellow Dr. Paul Joyce cautioned that the findings are based on animal research and should be interpreted with care. “Importantly, our findings do not prove that SNAC causes harm in humans,” Dr. Joyce stated. “However, they do display 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.”
The study highlights the complex interplay between medication, gut health, and overall well-being. Researchers are now calling for more comprehensive studies to assess the long-term effects of SNAC in humans, ensuring that the benefits of oral semaglutide are not overshadowed by unintended consequences. The team at Adelaide University plans to continue investigating the mechanisms by which SNAC impacts the gut microbiome and systemic inflammation.
Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
The next step in understanding the impact of SNAC will be human clinical trials to confirm whether the effects observed in animal models translate to people. Researchers are actively seeking funding to support these crucial studies. Share this article with anyone considering oral semaglutide, and join the conversation about gut health and weight management.
