Ozempic® and gallbladder problems

What the warning covers

Section 5.9 is titled Acute Gallbladder Disease. It names two conditions: cholelithiasis, meaning stones in the gallbladder, and cholecystitis, meaning inflammation of the gallbladder. The label says acute events of this kind have been reported both in trials of GLP-1 receptor agonists, the class Ozempic® belongs to, and after these medicines reached the market ^[1]. Canada carries the same warning and adds that gallbladder studies are indicated if either condition is suspected ^[3].

Gallstone figures in three documents

The US figure comes from two placebo-controlled trials in adults with type 2 diabetes over about 30 weeks. Canada’s comes from a seven-trial pool with a mixed placebo and active comparator group, and Europe gives a frequency class ^[1][2][3].

Reading those numbers

In the US trials every reported case was in an Ozempic® group, which is why the label treats the finding as a warning even though the rates are low. The higher US figure was on the lower dose, while in Canada’s larger pool the higher dose had the higher rate; with so few cases, the order between doses should not be over-read ^[1][3].

For scale, abdominal pain in the same US trials was reported by 4.6% on placebo and 7.3% and 5.7% on Ozempic®, so gallstones were a far rarer finding ^[1]. Section 6.2 lists cholecystitis and cholecystectomy (surgical removal of the gallbladder) among reports received after approval; because such reports are voluntary, their frequency cannot be reliably estimated ^[1].

What large studies found

A 2022 meta-analysis of 76 randomised trials with 103,371 patients found GLP-1 medicines linked to a higher risk of gallbladder or bile duct disease overall (relative risk 1.37), including gallstones (1.27) and cholecystitis (1.36). The rise was larger in weight-loss trials (2.29) than in diabetes trials (1.27), and was seen at higher doses and with longer use rather than at lower doses or shorter use ^[4].

A 2025 meta-analysis of 55 placebo-controlled trials with 106,395 participants reached a similar conclusion for gallstones (risk ratio 1.46, about 2 extra cases per 1,000 people) and found the effect looked more pronounced with weight-loss medicines and higher doses, although those subgroup differences were not statistically significant ^[5].

By contrast, a 2023 insurance-claims study of people without diabetes starting semaglutide or liraglutide for weight loss did not find a significantly higher risk of biliary disease than with bupropion-naltrexone (hazard ratio 1.50, confidence interval 0.89 to 2.53). Observational studies like this have their own limits, including uncertainty about why each medicine was prescribed ^[6].

Why it may happen

What the label supports: gallstones were more frequent on Ozempic® than on placebo in its trials, and acute gallbladder disease is a class warning for GLP-1 receptor agonists ^[1].

What has been proposed but not measured in the Ozempic® documents: the larger rise in weight-loss trials and at higher doses in the meta-analyses fits the idea that weight loss itself plays a part, but neither the label nor the studies cited here prove the mechanism ^[4][5].

General background: NIDDK explains that gallstones can form when bile contains too much cholesterol or bilirubin or too few bile salts, or when the gallbladder does not empty completely or often enough ^[7].

Other risk factors for gallstones

• Female sex, age over 40, a family history of gallstones, and Native American or Hispanic descent ^[8].
• Being overweight, and rapid weight loss from a very low-calorie diet or after weight-loss surgery ^[7][8].
• Diabetes, liver cirrhosis, pregnancy and taking birth control pills ^[8].
• Long-term nutrition through a vein and conditions that destroy many red blood cells ^[8].

How a gallbladder attack feels

NIDDK describes a gallbladder attack as pain in the upper right abdomen, sometimes lasting several hours, often after heavy meals and usually in the evening or at night. MedlinePlus adds that the pain may be constant or cramping, sharp or dull, can sit in the middle or right upper abdomen for at least 30 minutes, and may come with fever, yellowing of the skin and eyes, nausea and vomiting, or clay-coloured stools ^[7][8].

Most people with gallstones have no symptoms at all, and stones that do not block a duct generally do not need treatment, according to NIDDK ^[7]. Upper stomach pain also appears in the Ozempic® pancreatitis warning, as severe pain that may spread to the back; telling the two apart is for your clinician.

What may help

The Ozempic® documents give no specific prevention advice. NIDDK’s general guidance on lowering gallstone risk is a healthy eating plan with more high-fibre foods such as fruits, vegetables, beans and whole grains, fewer refined carbohydrates and less sugar, healthy fats such as fish oil and olive oil to help the gallbladder empty regularly, fewer fried foods and desserts, and regular physical activity ^[9].

NIDDK also notes that losing weight too quickly can raise gallstone risk, and asks people to talk with a health professional before changing their eating plan ^[9]. Weight-loss pace on Ozempic® is something to discuss with your prescriber rather than adjust yourself.

What to have ready when you call

Useful details are when the pain started and where it sits, how long it lasts, whether it follows meals, whether you have a temperature or chills, any change in the colour of your skin, eyes, urine or stools, and your current Ozempic® dose and when it was last increased. If you have had gallbladder problems before, say so.

Ozempic® is a registered trademark of Novo Nordisk A/S. PepLabo is not affiliated with or endorsed by Novo Nordisk.

When to get help