Two kinds of trial, two answers
The US label reports gallbladder figures from two sources. In the five glycemic control trials, which lasted at least 26 weeks, gallstones affected 0.3% and cholecystitis 0.2% of people on both Victoza® and placebo. [1] In LEADER, a cardiovascular outcomes trial in 9,340 adults with type 2 diabetes at high cardiovascular risk, most with established cardiovascular or kidney disease, the gap opened: 3.1% against 1.9% had an acute gallbladder event. [1] The label adds that most of these events required hospital treatment or removal of the gallbladder. [1]
| Measure | Victoza® | Placebo |
|---|---|---|
| Any acute gallbladder event, LEADER | 3.1% | 1.9% |
| Gallstones, LEADER | 1.5% | 1.1% |
| Acute cholecystitis, LEADER | 1.1% | 0.7% |
| Gallstones, glycemic trials | 0.3% | 0.3% |
| Cholecystitis, glycemic trials | 0.2% | 0.2% |
Rates over time and in other documents
Expressed per 1,000 years of follow-up, gallstones in LEADER occurred at 3.9 against 2.8, and acute cholecystitis at 2.9 against 1.9. [1] The European summary reports the same LEADER percentages, gives 0.4% for gallstones and 0.1% for cholecystitis across its long-term phase 3a trials, and rates both as uncommon, meaning between 1 in 1,000 and 1 in 100 people. [2] Canada’s LEADER table shows the same rows. [3]
After approval, the US label also lists gallstones needing surgery, cholecystitis, bile flow problems (cholestasis), raised liver enzymes and bilirubin, and hepatitis. [1] In the glycemic trials, mildly raised bilirubin without other liver test changes was seen in 4% on Victoza®, 2.1% on placebo and 3.5% on active comparators; its meaning is unknown. [1]
What a closer look at LEADER found
A post hoc analysis grouped every gallbladder and bile duct event reported in LEADER into uncomplicated gallstones, complicated gallstones, cholecystitis and bile duct obstruction. Events occurred in 141 of 4,668 people on liraglutide and 88 of 4,672 on placebo, a hazard ratio of 1.60, and the direction was the same in all four groups. [4] Gallbladder removal was more frequent on liraglutide, but among people who had an event, similar shares had surgery: 57% on liraglutide and 59% on placebo. [4] The authors note that LEADER was not designed to study gallbladder disease. [4]
What the class-wide research says
A 2022 meta-analysis of 76 randomised trials and more than 103,000 people found gallbladder or bile duct disease 37% more likely with GLP-1 medicines than with comparators. [5] The increase was larger in weight-loss trials than in diabetes trials (relative risks of 2.29 and 1.27), at higher doses and with longer use. [5] A 2025 meta-analysis of 55 placebo-controlled trials estimated about 2 extra cases of gallstones per 1,000 people. [7] Both pool several medicines, so they describe the class rather than Victoza® alone.
Why it might happen
Label position: the US label describes the events and asks for gallbladder studies when gallstones are suspected, but does not give a mechanism. [1]
Studied, not settled: in a 12-week trial in adults with overweight but without diabetes, liraglutide at the higher 3 mg weight-management dose did not reduce how much the gallbladder emptied after a meal, but the time to its maximum emptying was longer, about 151 minutes against 77 on placebo. [6] That dose and population differ from Victoza® users, and slower timing is a hypothesis, not proof.
General medicine: MedlinePlus lists rapid weight loss among risk factors for gallstones. [8]
Other risk factors in type 2 diabetes
MedlinePlus says gallstones are more common in women, people over 40, people who are overweight, those with a family history and people of Native American or Hispanic descent. [8] It also names diabetes itself, rapid weight loss, long periods of intravenous feeding and birth control pills. [8] Many people prescribed Victoza® carry several of these factors already, which is one reason a placebo comparison is needed to judge the medicine’s share.
Symptoms and what the sources describe
- The Victoza® Medication Guide lists pain in the upper stomach, yellowing of the skin or eyes, fever and clay-coloured stools, and asks you to tell your provider right away. [1]
- MedlinePlus describes gallbladder pain as lasting at least 30 minutes in the upper right or upper middle belly, often after a fatty meal, and sometimes spreading to the back or below the right shoulder blade. [9]
- Many people with gallstones have no symptoms at all; stones are often found during scans for other reasons. [8]
- MedlinePlus says avoiding rapid weight loss may help prevent gallstones in people with obesity. [8] Any plan to lose weight on Victoza® is worth discussing with your prescriber.
- Severe belly pain that does not go away can also be pancreatitis, which the label treats separately and urgently. [1]
Victoza® is a registered trademark of Novo Nordisk A/S. PepLabo is not affiliated with or endorsed by Novo Nordisk A/S.
When to get help
| Sign | Who to contact | How fast | Source |
|---|---|---|---|
| Severe belly pain that does not go away, possibly reaching the back, with or without vomiting | Stop Victoza® and call your provider straight away | Emergency | Medication Guide [1] |
| Severe pain in the upper right belly with fever | Seek medical attention right away | Emergency | MedlinePlus [9] |
| Upper stomach pain, yellow skin or eyes, fever or clay-coloured stools | Your provider, the same day | Today | Medication Guide [1] |
| Repeated pain after fatty meals, with nausea, bloating or indigestion | Book an appointment | At your next appointment | Canadian patient information [3]; MedlinePlus [9] |
| Gallstones found by chance on a scan while you use Victoza® | Discuss with your prescriber | At your next appointment | US label section 5.8 [1] |
