Trulicity® (dulaglutide) and gallbladder problems

How three regulators describe the risk

The US label places gallbladder disease among its warnings because gallstones and cholecystitis have been reported across GLP-1 receptor agonist trials and after approval. ^[1] Its numbers for Trulicity® come from REWIND alone. Tables 1 and 2, which pool the shorter blood sugar trials, have no gallbladder row at all. ^[1] The EU summary groups both conditions in a frequency class, and the Canadian monograph repeats the REWIND figures and names gallstones among less common reactions seen in trials. ^[3][4]

Making sense of 0.62 against 0.56

A patient-year is one person followed for one year. A rate of 0.62 per 100 patient-years means that, for every hundred people watched for a year, a little over half a gallstone event was recorded. Using time instead of a simple head count is fairer in a study where people stay for different lengths of time, as they did over five years of REWIND. ^[1]

The trial enrolled adults aged 50 or over with type 2 diabetes and either heart or blood vessel disease or several risk factors for it. Their average age was 66, 46% were women, the mean BMI was 32.3 and they had lived with diabetes for 10.5 years on average. ^[1] In the Trulicity® group, 53% were 65 or older and 10% were 75 or older, and the label reports no overall safety differences by age. ^[1] Two details limit how far the figures stretch: only the 1.5 mg dose was tested, and the label does not say whether the gap from placebo was statistically significant.

What studies of dulaglutide have added

Several kinds of evidence sit beyond the label, and each answers a different question. The broadest is a 2022 meta-analysis that pooled 76 randomised trials with 103,371 participants. Across GLP-1 medicines as a class, the risk of gallbladder or bile-duct disease was 37% higher than with placebo or other treatment (relative risk 1.37), gallstones 1.27 and cholecystitis 1.36. The rise was clearer at higher doses, with longer use and in weight-loss trials, while lower doses showed no difference. ^[5] These are class results, not a dulaglutide-specific estimate.

Real-world records come next. A 2026 retrospective cohort drew on a large health-records research network (TriNetX) and compared 39,140 adults with type 2 diabetes on a GLP-1 medicine with matched people who were not. After three years, gallstones, cholecystitis and gallbladder removal were all modestly more common; dulaglutide and semaglutide were each linked to more gallstones, while liraglutide and exenatide were not. ^[6] Records studies can find associations but not prove cause. A separate 2026 cohort comparing dulaglutide, semaglutide and tirzepatide head to head found similar rates of a combined outcome that included biliary disease, with residual confounding as its stated limitation. ^[9]

Voluntary reports give a third angle. An analysis of US adverse event reports from 2009 to 2025 found more gallbladder and bile-duct reports than expected for dulaglutide and three related medicines, but not for metformin or SGLT2 inhibitors used as comparisons. The median time from starting to the reported event ranged from about 147 to 320 days across the four medicines. ^[7] The authors stress that such reports cannot measure how often a problem happens or prove that the medicine caused it.

Finally, a published case describes a 72-year-old man who developed acute cholecystitis after 16 months on dulaglutide, without having lost weight; his gallbladder, found to be gangrenous, was removed, and he continued dulaglutide with no further biliary trouble over the next eight months. ^[8] It is a single patient and cannot be generalised.

Why the gallbladder could be involved

• What the label supports: gallbladder events are a class finding for GLP-1 receptor agonists, seen in trials and after approval, and Trulicity® is included. The label does not explain a mechanism. ^[1]
• What has been proposed but not measured for dulaglutide: the meta-analysis pattern, stronger with higher doses, longer use and weight-loss trials, suggests that dose, time on treatment and weight change may matter. ^[5] It does not show which of these drives the risk in people on Trulicity®, and the case above occurred without weight loss. ^[8]
• General medical knowledge: gallstones form when bile holds too much cholesterol or bilirubin, or the gallbladder does not empty fully or often enough. ^[12] Rapid weight loss, diabetes, obesity, being female and being over 40 all raise the background risk, so many people prescribed Trulicity® already carry several of them. ^[10]

Other reasons for pain under the right ribs

Most people with gallstones never notice them; these silent stones do not stop the gallbladder, liver or pancreas from working and usually need no treatment. ^[12] When a stone blocks a bile duct, the result is a gallbladder attack: pain in the upper right belly that can last several hours, often after a heavy meal and in the evening or at night. ^[12] Cholecystitis tends to cause steady pain lasting at least half an hour that may spread to the back or below the right shoulder blade, with fever, nausea or vomiting. ^[11]

NIDDK points out that gallstone pain can resemble appendicitis, stomach ulcers, pancreatitis and reflux disease, all of which need a doctor’s assessment. ^[12] A stone that blocks a duct can also inflame the pancreas. ^[10] Pancreatitis is a separate Trulicity® warning with its own signs, covered on the Trulicity® pancreatitis page. ^[1]

What the guidance says may help

There is no step that removes the risk, and MedlinePlus notes that in most people gallstones cannot be prevented. ^[10] For people living with obesity, it says avoiding rapid weight loss may help, and NIDDK adds that very low-calorie diets and weight-loss surgery raise gallstone risk. ^[10][13] NIDDK’s eating guidance favours fibre-rich foods such as fruit, vegetables, beans and whole grains, fewer refined carbohydrates and less sugar, healthy fats such as olive oil and fish oil, and fewer fried foods and desserts, and asks you to talk with a health professional before changing your eating plan. ^[13]

A 2025 Mayo Clinic Proceedings review lists biliary disease among the digestive effects of GLP-1 medicines and suggests starting symptom management with smaller, more frequent meals, enough fluids and fewer high-fat or high-sugar foods. ^[14] Before you start Trulicity®, MedlinePlus asks you to tell your doctor about any gallbladder disease, and the Medication Guide asks you to report the four warning signs right away. ^[15][2]

Trulicity® is a registered trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Eli Lilly and Company.

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