SNAC Ingredient in Wegovy and Ozempic Raises Gut Health Concerns

The pill forms of popular weight loss medications Wegovy and Ozempic, containing the active ingredient semaglutide, rely on salcaprozate sodium (SNAC) to enhance absorption. Still, a new study from the University of Adelaide suggests that SNAC may have unintended consequences for gut health, prompting researchers to call for further investigation into its long-term effects.

How SNAC Works

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is easily broken down by stomach acid. SNAC temporarily regulates stomach acidity and increases the permeability of the stomach wall, allowing semaglutide to enter the bloodstream before it’s degraded [1]. Without SNAC, oral semaglutide would be significantly less effective.

Study Findings in Animal Models

Researchers at the University of Adelaide conducted a 21-day study using a mouse model to examine the effects of semaglutide, SNAC, and a combination of both on gut microbiota and metabolic function [1]. The study, published in the Journal of Controlled Release, revealed several key changes in the SNAC-exposed group:

• Reduced Beneficial Gut Bacteria: Significant depletion of primary fermenters, including Muribaculaceae (–62%) and Bacteroidaceae (–77%) [3].
• Decreased Butyrate Production: Lower levels of butyrate, a short-chain fatty acid essential for gut health and inflammation control, decreased by 77% with SNAC and 75% with the combination treatment [1].
• Increased Inflammation: Elevated levels of inflammatory markers, such as TNF-α and IL-6, were observed in the bloodstream [1].
• Liver Changes: Increased liver weight, potentially indicating low-grade inflammation [3].
• Reduced Cecum Size: A smaller cecum, the part of the intestine responsible for fiber breakdown and protective compound production [3].
• Lower BDNF Levels: Reduced levels of brain-derived neurotrophic factor (BDNF), a protein associated with cognitive function [1].

What This Means for Human Health

Researchers emphasize that the study was conducted on mice over a relatively short period and does not definitively prove harm to humans. However, the findings raise important questions about the long-term effects of daily SNAC exposure, especially given the increasing global use of oral semaglutide [4]. Most safety data currently focus on the active drug (semaglutide) rather than the absorption enhancer (SNAC), highlighting the need for targeted research to clarify SNAC’s independent effects on the gut microbiome, inflammation, and overall systemic health [4].

Future Directions

The research team recommends further long-term studies in humans to fully understand the implications of SNAC exposure. They too point to the development of next-generation oral obesity drugs that utilize “small molecule” treatments, which may not require absorption enhancers like SNAC [1]. Researchers stress that medications should be viewed as a complement to a healthy diet and regular physical activity, and a comprehensive understanding of all drug components is crucial for long-term metabolic health.