Do GLP-1 medicines raise the risk of gallbladder problems?

Why this study matters

Gallstones and gallbladder inflammation are known to be more common during rapid weight loss of any kind. There has been debate about whether GLP-1 medicines add to that risk on their own. This review is the largest pooled look at randomized trials on the question. Canadian readers who use or are considering semaglutide (Wegovy, Ozempic), liraglutide (Saxenda, Victoza) or a related medicine will often see this study quoted.

Who was in the study

This was a meta-analysis, which combines the results of many trials into one estimate. The researchers searched four medical databases and trial registries up to mid-2021 and found 76 randomized clinical trials that compared a GLP-1 receptor agonist with placebo or with a non-GLP-1 medicine in adults. Together the trials included 103371 people. The average age was 57.8 years, and 41868 people (40.5%) were women. The trials covered type 2 diabetes, weight loss and other conditions. The summary we reviewed does not report how long the trials lasted.

What the researchers did

Two reviewers independently pulled the data from each trial and rated its quality using a standard risk-of-bias tool. They calculated pooled relative risks. A relative risk (RR) compares how often something happened in the medicine group with how often it happened in the comparison group. An RR of 1 means no difference. An RR above 1 means the event was more common in the medicine group.

The main outcome was a combined measure of gallbladder or biliary disease. Biliary disease means disease of the bile ducts, the tubes that carry bile from the liver and gallbladder to the gut. Secondary outcomes included gallstones (cholelithiasis), gallbladder inflammation (cholecystitis), gallbladder removal (cholecystectomy), biliary disease and biliary cancer. The researchers also rated how certain the evidence was using the GRADE system.

What they found

Across all 76 trials, being assigned to a GLP-1 medicine was associated with a higher risk of gallbladder or biliary disease, with an RR of 1.37 and a 95% confidence interval of 1.23 to 1.52 (R32-C117). A confidence interval is the range in which the true value is likely to sit. Because the whole range is above 1, the increase was statistically clear.

The risk was higher in weight-loss trials than in diabetes trials, higher with higher doses than lower doses, and higher with longer use than shorter use. For lower doses and shorter use, the confidence intervals include 1, meaning no clear increase was seen in those subgroups.

Side effects and people who stopped

This review looked only at gallbladder and biliary outcomes. It does not report other side effects or how many people stopped treatment in the included trials.

What this study does not tell you

• The summary we reviewed reports relative risks only. It does not say how many people in each group actually had a gallbladder event, so the size of the risk for any one person cannot be read from this page.
• The trials used different medicines, doses, durations and populations, and pooling them blurs those differences.
• Rapid weight loss itself is linked to gallstones, and the analysis cannot fully separate the effect of the medicine from the effect of losing weight.
• Our summary is based on the abstract and extracted data. Two attempts to retrieve the full paper were unsuccessful.
• The summary we reviewed does not state who funded the review.

What it means in Canada

This review supports the idea that gallbladder problems are a real, if uncommon, risk with GLP-1 medicines, and that the risk was larger in trials for weight management than in diabetes trials. It does not say how likely a gallbladder problem is for any individual. For how these medicines are used in Canada, see semaglutide in Canada and tirzepatide in Canada. For coverage questions, see public drug coverage by province.

Related reading

Other studies in this library that bear on the same question.

Source