Bold warning: a seemingly convenient weight-loss pill could carry surprising downsides that many overlook. But here’s where the story gets controversial…
The new oral form of the popular GLP-1 drugs, designed to help people lose weight, contains a compound that may bring about troublesome side effects. Traditionally, semaglutide—the active ingredient in Ozempic and Wegovy—was delivered via weekly injections into the subcutaneous tissue of the abdomen, thigh, or upper arm. To accommodate needle-averse patients, manufacturers developed a daily semaglutide pill that aims to deliver similar results without injections.
Novo Nordisk began selling the Wegovy pill in early January, with the Ozempic pill anticipated to hit the market in spring. While injections provide direct entry into the bloodstream, the pill relies on salcaprozate sodium (SNAC). SNAC helps semaglutide survive the harsh environment of the stomach and reach the bloodstream.
Researchers at the University of Adelaide explored what happens when SNAC is taken repeatedly. Their goal was to understand how long-term exposure to SNAC might affect the gut microbiota, metabolic function, and related health markers.
Lead author Amin Ariaee, a PhD candidate at Adelaide University, emphasizes the need to look beyond the active drug as oral versions become more common. “These medicines are highly effective and help many people, but with daily oral use, we must understand what repeated exposure to all ingredients in the pill means for the body,” he notes.
In a 21-day study, several notable changes were observed:
- A decline in beneficial gut bacteria responsible for breaking down dietary fiber
- A reduction in short-chain fatty acids, which support the intestinal barrier, help regulate inflammation, and assist immune function
- An increase in inflammatory markers in the blood
- An increase in liver weight
- A smaller cecum, a section of the large intestine where gut bacteria process fiber and produce protective compounds
- Lower levels of a protein linked to cognitive impairment
Ariaee points out that the convenience of a tablet comes with unique risks. “While SNAC enables semaglutide to be taken orally, our study shows it’s also associated with shifts in potentially harmful gut bacteria, elevated inflammatory markers, and depletion of proteins linked to cognitive health,” he says. He cautions that the study does not prove SNAC is harmful to humans, but it does show that the compound can affect the body beyond helping semaglutide work, warranting further investigation.
Meanwhile, Novo Nordisk’s first semaglutide pill has already launched, and a competing daily pill from Lilly, Orforglipron, is expected to gain FDA approval this spring. Both pills come with gastrointestinal side effects and have not matched the potency of injections, yet the potential market impact remains enormous. An added advantage is that pills don’t require refrigeration like some GLP-1 injections, simplifying storage and shipping.
Because pills offer greater convenience and may reduce costs, the study authors stress the importance of understanding how consistent SNAC exposure could affect patients over time. “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 drug,” says Senior Research Fellow Dr. Paul Joyce.
Would you consider oral GLP-1 medications as a viable alternative to injections, or would concerns about SNAC and gut health sway your decision? Let us know your thoughts in the comments.
