Semaglutide Shows Promise for Osteoarthritis While SNAC Ingredient Raises Safety Questions

Semaglutide can ease symptoms of osteoarthritis and thicken cartilage between bones in both mice and people, according to research reported February 9 in Cell Metabolism. The findings suggest the drug acts directly on joints rather than simply reducing symptoms through weight loss.

In mice with osteoarthritis, one group received semaglutide while another had food intake restricted to match the weight loss of the treated group. Both groups shed weight, but only the treated mice saw joint-based benefits. These mice had less pain, less broken-down cartilage and more cartilage growth. The results suggest that weight loss isn't driving semaglutide's benefits.

A small clinical trial in obese people with knee osteoarthritis showed similar results. After six months on a low dose of semaglutide plus hyaluronic acid, a lubricant made by the body, participants' knee function improved. MRI exams revealed a 17 percent increase in cartilage thickness in people on semaglutide, compared with a less than 1 percent increase in people on just hyaluronic acid. The trial included 20 people; a larger study could help confirm the results.

Thicker cartilage suggests the tissue is being rebuilt. More cartilage means more cushion, which means less bone-on-bone grinding and less pain. Lab experiments suggest the drug scales up energy production in cartilage, which could give the tissue more fuel to heal.

Osteoarthritis is the most common form of arthritis, affecting more than 500 million people worldwide. The disease can affect the hands, knees, hips and other joints, causing severe pain as cartilage wears away and tissues inflame. There's no cure, and no medications that prevent it from becoming worse.

In 2024, a clinical trial in people with obesity reported that the drug improved joint pain and function. Doctors assumed those benefits were due to weight loss.

Meanwhile, separate research from Adelaide University raises questions about salcaprozate sodium (SNAC), the ingredient used to help semaglutide tablets get absorbed. In a 21-day animal study, repeated SNAC exposure was linked to shifts in the gut microbiome and signs of broader biological changes that reached beyond the digestive tract.

This was the first in vivo study designed to systematically track how ongoing SNAC exposure affects gut microbes, what those microbes produce, and related metabolic signals. Compared with controls, the researchers observed fewer beneficial gut bacteria involved in breaking down dietary fiber, lower levels of short-chain fatty acids, compounds that help support the gut lining and play a role in inflammation control, higher levels of inflammatory markers in the blood, increased liver weight, which can be consistent with low-grade inflammation, a smaller cecum, and reduced levels of a brain-derived protein associated with cognitive impairment.

The study does not show that SNAC causes harm, and it does not establish what these signals would mean in people, but it does raise a practical question: what happens when an ingredient designed for delivery becomes part of a daily routine for years.

In oral semaglutide, SNAC is included to protect the drug from enzymatic degradation in the stomach and help it cross into the bloodstream. Without SNAC, oral semaglutide would not work. The United States approved a tablet version of Wegovy late last year. Because pills are expected to be less expensive and more convenient than injections, daily and long term exposure to SNAC is likely to rise significantly.

Around 890 million adults and 160 million children worldwide are living with obesity, which equals roughly one in eight people. Among OECD nations, the United States has the highest obesity rate, with 43% of people aged 15+ affected. Australia ranks sixth at 31%, compared with the OECD average of 25%. In Australia, prescriptions for medications such as Ozempic and Wegovy have increased sharply in recent years.

The findings were published February 9, 2026 in Journal of Controlled Release with DOI: 10.1016/j.jconrel.2026.114711.