Downside to dropping pounds?
The new pill form of popular GLP-1 drugs contains a compound that could cause troubling side effects.
Historically, semaglutide, the active ingredient in Ozempic and Wegovy, has been administered via weekly injections into the fatty tissue just under the skin of the stomach, thigh or upper arm.
But due to consumer aversion to needles, manufacturers have developed a daily semaglutide pill that promises to deliver similar effects sans stab.
Novo Nordisk began selling the Wegovy pill in early January, while the Ozempic pill is expected in the spring.
While injection allows the drug to enter the bloodstream directly, the pill’s ability to work depends on something called salcaprozate sodium (SNAC), a compound that ensures semaglutide survives in the stomach and reaches the bloodstream.
Using animal models, researchers at the University of Adelaide sought to establish how repeated exposure to SNAC influences the gut microbiota, metabolic function and related health markers.
“These medicines are highly effective and are helping many people 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,” said lead author Amin Ariaee, a PhD candidate at Adelaide University.
In a 21-day period, the team recorded the following changes.
- Less of the good gut bacteria that breaks down dietary fiber
- Fewer short-chain fatty acids, which strengthen the intestinal barrier, reduce inflammation and also help with immune system function
- More inflammatory markers in the blood
- Higher liver weight
- A smaller cecum, part of the large intestine. The cecum is where gut bacteria breaks down fiber and produce protective compounds
- Lower levels of a protein associated with cognitive impairment
According to Ariaee, the ease of taking a tablet comes with a different set of consequences.
“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,” he said.
He maintains that the study does not prove the SNAC is inherently harmful to humans, but rather that the compound affects the body beyond facilitating the function of semaglutide, and further research is warranted.
While Nordisk’s first semaglutide pill already launched, a daily pill from Lilly, known as Orforglipron is expected to be approved by the FDA this spring.
Both pills come with some gastrointestinal side effects — and they didn’t deliver the same dramatic results as the injectables — but drugmakers say the potential is still huge.
On top of ditching the needles, the pills don’t need to be refrigerated like other GLP-1s, making them far easier to store and ship.
Because pills are more convenient and potentially less cost-prohibitive than injections, study authors maintain that it is essential to understand how consistent exposure to SNAC can affect patients.
“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,” said Senior Research Fellow Dr. Paul Joyce.
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