By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
Gallstones and GLP-1 drugs: the short answer
Gallstones are one of the side effects worth knowing about when you are treated with GLP-1 drugs. These medications, such as Wegovy and Mounjaro, have transformed the treatment of obesity. Alongside their major benefits, they modestly raise the risk of gallstones and of inflammation of the gallbladder. In absolute numbers, this means a small number of additional cases.
In this article I have gathered the key studies. What is the mechanism? Who is at particularly high risk? When does an ultrasound make sense? And how can you lower the risk without giving up an effective treatment?
The gallbladder and gallstones: a quick background
The gallbladder is a small sac beneath the liver. It stores bile, a fluid the liver produces that helps digest fats. After a meal, especially a meal containing fat, the gallbladder contracts and empties bile into the intestine.
Gallstones form when bile becomes oversaturated with cholesterol, or when it sits in the gallbladder for a long time. This is not a rare problem. According to guidelines from the European Association for the Study of the Liver (EASL), up to 20% of the population in Europe has gallstones. Most stones stay silent for life. Symptoms develop at a rate of 1% to 4% a year.
GLP-1 drugs mimic a natural satiety hormone produced in the gut. Semaglutide is the active ingredient in Ozempic and Wegovy. Tirzepatide, the active ingredient in Mounjaro, also acts on the receptor for the hormone GIP. I explain the differences between the drugs in my article on Mounjaro vs. Wegovy.
What studies have found about gallstones
In 2022, JAMA Internal Medicine published a large meta-analysis, a combined analysis of many studies. It included 76 controlled trials and 103,371 participants, most of them with type 2 diabetes. Treatment was associated with a 37% increase in the risk of gallbladder and biliary disease (relative risk 1.37). The risk of gallstones rose 1.27-fold, and the risk of gallbladder inflammation 1.36-fold.
Three findings stood out. First, the risk was higher in weight-loss trials (relative risk 2.29) than in diabetes trials (1.27). Second, the risk rose at high doses (1.56) but not at low doses (0.99). Third, it rose when treatment lasted a long time (1.40).
A more recent meta-analysis in Gastroenterology, from 2025, included 55 trials and 106,395 participants. The drugs raised the risk of gallstones (relative risk 1.46), which works out to 2 additional cases for every 1,000 patients treated. They had no clear effect, however, on other biliary events.
Wegovy, Mounjaro and liraglutide: the data
In the STEP 1 trial, gallbladder disorders, mainly stones, occurred in 2.6% of patients on semaglutide 2.4 mg, compared with 1.2% in the placebo group. Put another way, about 3 in 100 patients versus about 1 in 100.
The SELECT trial enrolled 17,604 people with heart disease and excess weight but without diabetes. According to an analysis of adverse events in SELECT, serious gallbladder events occurred in 1.2% of women on semaglutide, compared with 0.9% on placebo. In men, the rates were 1.3% versus 1.1%.
The SUSTAIN-6 trial enrolled 3,297 people with type 2 diabetes. There, gallbladder disorders occurred in 3.9% of patients on the 0.5 mg dose and in 3.2% on the 1.0 mg dose. In the matching placebo groups, the rates were 4.6% and 2.8%. In other words, this trial showed no clear difference.
For tirzepatide, manufacturer data from the SURMOUNT-1 and SURMOUNT-2 trials show gallstones reported in 1.1% of patients, compared with 1% on placebo. Gallbladder inflammation occurred in 0.7% versus 0.2%, and gallbladder removal in 0.2% versus zero.
A similar signal appears in diabetes as well. The LEADER trial enrolled 9,340 people with diabetes. Acute gallbladder disease occurred in 141 of 4,668 patients on liraglutide, compared with 88 of 4,672 on placebo. That is a 1.60-fold higher risk, even though weight loss in diabetes trials is moderate.
Why gallstones form during treatment
There is no single cause. Several processes work in parallel and reinforce one another.
Rapid weight loss. When the body breaks down fat quickly, the liver secretes a lot of cholesterol into the bile. The bile becomes oversaturated, crystals form, and stones grow from them. This has been known for decades, including after bariatric surgery and very-low-calorie diets. According to EASL, the risk rises significantly with weight loss of more than 1.5 kg a week. I have written about the dangers of losing weight that fast in my article on rapid weight loss.
A slower-working gallbladder. Studies of liraglutide showed that the drug lengthens the time it takes the gallbladder to empty fully. It also affects gut hormones that regulate gallbladder filling.
Less food, fewer contractions. When you eat little, and especially little fat, the gallbladder contracts less often. As a result, bile sits in it for a long time.
Who is at higher risk
According to the studies, the risk is higher with treatment for weight loss, at high doses and with long-term treatment. It also rises with rapid, large weight loss, mainly in the first months. Female sex and older age are well-known risk factors for gallstones too, alongside obesity itself.
It’s important to remember that not every stone found during treatment was caused by the drug. Gallstones are very common in people with obesity even without medication. Most patients do not have an ultrasound before starting treatment, so some of the stones were already there. The picture is most likely a combination of baseline risk, weight loss and a modest direct effect of the drug.
Do you need an ultrasound before treatment?
At present, guidelines do not recommend a routine ultrasound for every patient before treatment. Most silent stones stay silent, and stones without symptoms usually do not need surgery. What’s more, finding a silent stone by chance can lead to unnecessary tests and anxiety.
That said, an ultrasound makes sense for anyone who has had upper abdominal pain, gallbladder inflammation or pancreatitis in the past. It is also appropriate for people with unexplained abnormal liver enzymes. Finally, it is useful in a high-risk patient who is planning substantial weight loss. In other words, the recommended approach is selective, not routine.
How to lower the risk of gallstones
Gradual dose escalation. The risk is linked to the dose and to the pace of weight loss. So it’s wise to step up gradually, without skipping steps and without rushing to the maximum dose. I have written about this in my article on target-based dosing of GLP-1 drugs.
Regular meals with a little healthy fat. The gallbladder contracts in response to fat. Olive oil, nuts or avocado at every meal encourage regular emptying. A meta-analysis of 13 trials found that higher-fat weight-loss diets reduced gallstones compared with low-fat diets.
Ursodeoxycholic acid (UDCA). This is a natural bile acid that reduces cholesterol saturation in bile. The same meta-analysis included 1,836 people who lost weight through diet or surgery. UDCA reduced the risk of gallstones by about two-thirds (relative risk 0.33). EASL recommends temporary UDCA, at least 500 mg a day, during rapid weight loss and until weight stabilizes. However, there are still no trials in patients taking GLP-1 drugs. The decision is therefore individual and suits mainly high-risk patients.
Avoiding yo-yo dieting. According to EASL, repeated swings in weight raise the risk of gallstones in their own right. So repeatedly stopping and restarting treatment is not a good idea.
Why you shouldn’t give up on treatment
The absolute risk is small. In the SELECT trial, the difference in serious gallbladder events was about 0.2-0.3 percentage points. In the same trial, major cardiovascular events fell from 8.0% to 6.5%, a 20% reduction. In other words, the number of heart events prevented is several times greater than the number of additional gallbladder cases. Moreover, stopping the drug does not eliminate the risk. Obesity itself is a risk factor for gallstones, and so are surgery and extreme diets.
Warning signs and other points
Severe, persistent pain in the upper right abdomen, especially after a meal, calls for a visit to the doctor. Sometimes the pain radiates to the back or the right shoulder. Fever, vomiting that doesn’t go away, yellowing of the skin or eyes, and dark urine also require medical evaluation. By contrast, mild nausea in the days after an injection is common and does not point to a gallbladder problem. You’ll find more on this in my guide to Mounjaro side effects.
Treatment can continue after the gallbladder has been removed. In addition, GLP-1 drugs slow stomach emptying, so before any surgery it’s important to tell the anesthesia team. At present there are no direct data showing that one drug is safer than another where the gallbladder is concerned.
The bottom line: gallstones and getting treatment right
GLP-1 drugs modestly raise the risk of gallstones and of gallbladder inflammation. The risk is higher with treatment for weight loss, at high doses and with rapid weight loss. In absolute numbers it is a small increase, dwarfed by the metabolic and cardiovascular benefits. Gradual dose escalation, a moderate pace of weight loss and regular meals reduce the risk. Ultimately, the right path is not to give up on treatment, but to manage it well.
The information in this article is general and is not a substitute for personal medical advice. Any decision about treatment, testing or prevention should be made together with your treating physician.
References
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
Can people with gallbladder disease or gallbladder removal take Zepbound (tirzepatide)?
EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones
