'UDCA prevents gallstones in patients undergoing rapid weight loss with GLP-1 drugs'

As GLP-1 obesity drugs -- such as Wegovy and Saxenda -- gain popularity for their effectiveness in weight loss, concerns are rising over adverse reactions such as cholelithiasis linked to rapid weight reduction.

Daewoong Pharmaceutical said Friday that Ursa Tablet 300mg (ursodeoxycholic acid, UDCA), a prescription drug, is drawing attention as a preventive option for gallstones caused by swift weight loss.

In Korea, Ursa Tablet 300mg is indicated to prevent gallstone formation in obese patients who lose weight rapidly. Ursa Capsule 50mg and 100mg are over-the-counter (OTC) drugs for enhancing liver function. 

Rapid weight loss increases cholesterol secretion by the liver while reducing gallbladder contractions due to decreased food intake. This causes bile to stagnate, leading to cholesterol supersaturation and the formation of crystals that can develop into gallstones.

Multiple studies have linked rapid weight loss from low-calorie diets to an increased risk of gallstones. Research by Stinton LM et al., published in Gut and Liver, found that 30 to 71 percent of patients who lost weight rapidly developed gallstones -- particularly those losing more than 1.5 kilograms per week, which significantly elevated the risk.

The U.S. FDA has reviewed data from its adverse event reporting system (FAERS) and identified studies suggesting that GLP-1 drugs may increase the risk of gallbladder disease, including gallstones. The FDA requires manufacturers of GLP-1 shots to include warnings in their labeling about the increased risk of gallstones associated with rapid weight loss.

The scientific community has also raised concerns. A 2022 study published in JAMA Internal Medicine reported that GLP-1 drugs can impair gallbladder motility, potentially increasing the risk of gallbladder and bile duct diseases, including gallstones.

Daewoong said Ursa (300 mg), which lowers cholesterol in bile and promotes bile flow, is recognized as a preventive treatment targeting the core mechanism of gallstone formation.

Its effectiveness in preventing gallstones during rapid weight loss has been confirmed by several international studies. 

A 1995 study by Shiffman M L et al., published in Annals of Internal Medicine, found that obese patients on a very low-calorie diet who took UDCA (300 mg twice daily) had a gallstone incidence of just 3 percent—significantly lower than the 28 percent seen in the placebo group.

In the international journal Digestive Diseases and Sciences, Dr. Marks JW and colleagues reported in 1996 that patients taking UDCA during rapid weight loss on a very low-calorie diet maintained gallbladder contractility and experienced reduced cholesterol saturation in bile, acccording to Daewoong. These findings suggest that Ursa may offer a practical solution to prevent gallstone formation associated with rapid weight loss, the company said.

"These studies are dated because UDCA’s effectiveness in preventing gallstones during rapid weight loss has long been established," a Daewoong spokesperson said.

Ursa’s gallstone prevention effect has also been demonstrated in gastric cancer patients following gastrectomy. Professor Lee Sang-Hyub at Seoul National University Hospital and his team found in 2024 that UDCA significantly reduced the incidence of gallstones in this high-risk group.

Patients who undergo gastrectomy often experience rapid weight loss due to reduced food intake and altered digestion from decreased stomach volume. Additionally, vagus nerve transection during surgery can impair gallbladder motility, causing bile stasis and crystallization, which frequently leads to gallstone formation. As a result, prophylactic use of UDCA is considered an effective strategy to reduce this risk.

According to Professor Lee’s research team, the five-year incidence of gallstones was only 8–10 percent in the group receiving 300 mg of UDCA, compared to over 20 percent in the placebo group. The findings suggest that UDCA effectively prevents gallstones long-term by reducing bile stasis and cholesterol crystallization resulting from impaired gallbladder motility after surgery, Daewoong said.