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Do GLP-1 medicines cause gallbladder problems or pancreatitis? What the research found

Gallstones and pancreatitis are two of the side effects people worry about most on Ozempic, Wegovy, Mounjaro and Zepbound. Here is what the trials and drug labels report, in absolute numbers, and which symptoms the labels say need medical attention.

By 7 min read
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The short version
  • GLP-1 medicines raise the risk of gallbladder problems, but absolute rates are low: in Wegovy weight-loss trials, gallstones were reported in 1.6% of adults on the injection vs 0.7% on placebo.7
  • Across 76 randomized trials, GLP-1 use was linked to a 37% higher relative risk of gallbladder or bile duct disease, more so at higher doses, with longer use and in weight-loss trials.1
  • Pancreatitis was rare in trials, and large pooled analyses did not find a clear increase. The labels still warn about it and list the symptoms that need urgent attention.4,5,8

Do GLP-1 medicines cause gallbladder problems?

Yes, they raise the risk, and the US labels for all four main GLP-1 medicines include a warning on acute gallbladder disease.7,8,9 The two problems seen most are gallstones (cholelithiasis) and an inflamed gallbladder (cholecystitis). The table shows how often they were reported in the trials behind each label.

Medicine and trialsGallstonesGallbladder inflammationGallbladder removed
Semaglutide injection (Wegovy), adult weight-loss trials1.6% vs 0.7%0.6% vs 0.2%not reported
Semaglutide tablet (Wegovy), adult weight-loss trials2.5% vs 1%not reportednot reported
Tirzepatide (Zepbound), SURMOUNT-1 and -2 pooled1.1% vs 1%0.7% vs 0.2%0.2% vs 0%
Tirzepatide (Mounjaro), type 2 diabetes trials pooledAcute gallbladder disease (gallstones, biliary colic, removal): 0.6% vs 0%
 Medicine vs placebo. Source: US prescribing information, sections 5 and 6.7,8,9

The Wegovy label also reports higher rates in teenagers aged 12 and older: gallstones in 3.8% on semaglutide vs 0% on placebo.7

The STEP trials of semaglutide 2.4 mg

A 2026 pooled analysis looked at gallbladder events across four placebo-controlled STEP trials, 3,683 adults with overweight or obesity. In STEP 1 alone there were 34 gallbladder-related events among 1,306 people on semaglutide vs 8 among 655 on placebo over 68 weeks.2

1.92gallbladder events per 100 patient-years on semaglutide 2.4 mg (STEP 1, 2, 3, 5)
0.82per 100 patient-years on placebo in the same trials

That is about twice the risk (risk ratio 2.08). The authors estimate roughly one extra gallbladder event for every 90 to 100 people treated for a year. Most events were gallstones; inflammation and removal were rare.2 One limit: trials counted symptoms people reported, not routine ultrasound, so silent gallstones were missed.

What the big meta-analysis found

The largest review so far, published in JAMA Internal Medicine in 2022, pooled 76 randomized trials with 103,371 adults taking various GLP-1 medicines for diabetes, weight loss or other conditions.1

  • Overall, GLP-1 use was linked to a higher risk of gallbladder or bile duct disease (relative risk 1.37).
  • The risk was higher in the 13 weight-loss trials (relative risk 2.29) than in diabetes and other trials (1.27).
  • It was higher at higher doses (1.56) and with longer use (1.40). At lower doses and shorter use there was no clear increase.

For tirzepatide (Zepbound, Mounjaro), a 2023 meta-analysis of 9 trials with 9,871 people found a higher risk of the combined gallbladder or biliary outcome vs placebo or basal insulin (relative risk 1.97).3

Illustration of a magnifying glass over smooth pebbles.

Why do GLP-1 drugs cause gallstones?

Two reasons are discussed. First, weight loss itself. The Wegovy label says substantial or rapid weight loss can raise the risk of gallstones, but adds that gallbladder disease was still more common on Wegovy than placebo even after accounting for how much weight people lost.7 Second, the STEP pooled analysis notes that GLP-1 receptors on the gallbladder can slow how well it empties, which lets bile sit.2 Both may act together, which fits the higher risk seen in weight-loss trials.

The Zepbound label states that acute gallbladder events were associated with weight reduction.8 If you are losing weight quickly, see what to eat on a GLP-1 for the research on eating patterns, and talk to your care team about your pace.

Do GLP-1 medicines cause pancreatitis?

Acute pancreatitis, including fatal and non-fatal severe forms, has been observed with GLP-1 medicines, and every label carries a warning.7,8,9 But in controlled trials it was uncommon, and in some trials it was as common on placebo.

Medicine and trialsMedicinePlacebo or comparator
Wegovy, adult weight-loss trials4 people (0.2 per 100 patient-years)1 person (under 0.1)
Zepbound, SURMOUNT-1 and -2 pooled0.2% (0.14 per 100 years)0.2% (0.15 per 100 years)
Ozempic, type 2 diabetes trials7 people (0.3 per 100 patient-years)3 people (0.2)
Mounjaro, type 2 diabetes trials13 people (0.23 per 100 years)3 people (0.11)
 Cases confirmed by an independent committee. Source: US prescribing information, section 6.1.7,8,9

Pooled analyses of trials

  • Heart outcome trials (2020). A meta-analysis of the large cardiovascular outcome trials of GLP-1 medicines, where pancreatitis was formally checked, found no significant increase (rate ratio 1.05, 95% CI 0.78 to 1.41).4
  • Weight-loss studies (2026). A meta-analysis of 52 studies in people with obesity found no significant link with pancreatitis (odds ratio 1.29, 95% CI 0.91 to 1.84).5
  • Tirzepatide (2026). Across 19 randomized trials with 15,471 people, acute pancreatitis occurred in 0.22%, with no difference between the 5, 10 and 15 mg doses.6 An earlier 2023 review also found no significant increase (relative risk 1.46, not statistically significant).3

"No significant increase" is not the same as "no risk". Pancreatitis is rare, so even large trials can miss a small effect. That is why the labels keep the warning.

Symptoms to get checked, according to the labels

These are the labels' instructions to patients, not personal advice. Your care team knows your history.

  • Possible pancreatitis. Severe pain in the stomach area that will not go away, with or without nausea or vomiting. The pain may spread to the back. The Wegovy and Zepbound labels tell patients to stop the medicine and call their healthcare provider right away.7,8
  • Possible gallbladder problems. Pain in the upper stomach, fever, yellowing of the skin or eyes (jaundice), or clay-colored stools. The labels say to contact your healthcare provider.7,8
Mild nausea and stomach upset are common on GLP-1s, especially after a dose increase (see GLP-1 nausea and stomach side effects). Pain that is severe, does not go away, or comes with fever or yellow skin is different. If you have severe abdominal pain, seek medical care promptly; in an emergency, call your local emergency number.

What these numbers can and cannot tell you

The label and trial figures come from randomized, placebo-controlled trials, the strongest kind of evidence for side effects. But trials enroll selected people and last one to two years. They cannot tell you your own risk, which depends on your own health history, such as past gallstones or pancreatitis. Bring your history to your prescriber, and see GLP-1 long-term results for what longer studies show.

Common questions

Does Ozempic cause gallbladder issues?

Semaglutide, the medicine in Ozempic and Wegovy, raises the risk of gallstones, but the absolute risk is small. In Wegovy weight-loss trials in adults, gallstones were reported in 1.6% of people on the injection vs 0.7% on placebo, and gallbladder inflammation in 0.6% vs 0.2%.

Do GLP-1 medicines lead to gallbladder removal?

Sometimes, but rarely in trials. In the pooled SURMOUNT-1 and SURMOUNT-2 weight-loss trials of tirzepatide (Zepbound), gallbladder removal (cholecystectomy) was reported in 0.2% of people on the medicine and in no one on placebo.

Why do GLP-1 drugs cause gallstones?

The Wegovy label says substantial or rapid weight loss can raise the risk of gallstones, but gallbladder disease was still more common on Wegovy than placebo after accounting for weight loss. A 2022 meta-analysis of 76 randomized trials found the risk was higher at higher doses, with longer use and in weight-loss trials.

What is the risk of pancreatitis on a GLP-1?

Acute pancreatitis was rare in trials. In the pooled SURMOUNT-1 and SURMOUNT-2 trials, it occurred in 0.2% of people on tirzepatide and 0.2% on placebo, and in Wegovy weight-loss trials there were 0.2 cases per 100 patient-years vs less than 0.1 on placebo.

What are the symptoms of pancreatitis on a GLP-1?

The US labels for Wegovy and Zepbound describe severe stomach pain that will not go away, sometimes spreading to the back, with or without nausea or vomiting. The labels tell patients to stop the medicine and call their healthcare provider right away if this happens.

Sources

  1. He L, Wang J, Ping F, et al. Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Intern Med. 2022;182(5):513-519. doi:10.1001/jamainternmed.2022.0338 · Full text (PMC)
  2. Ukkonen M, Kivivuori A, Starckjohann P, et al. Gallbladder-Related Adverse Events With Semaglutide 2.4 mg: Pooled Analysis of Placebo-Controlled STEP Trials. Diabetes Obes Metab. 2026;28(10):9701-9703. doi:10.1111/dom.71087 · Full text (PMC)
  3. Zeng Q, Xu J, Mu X, et al. Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023;14:1214334. doi:10.3389/fendo.2023.1214334 · Full text (PMC)
  4. Abd El Aziz M, Cahyadi O, Meier JJ, et al. Incretin-based glucose-lowering medications and the risk of acute pancreatitis and malignancies: a meta-analysis based on cardiovascular outcomes trials. Diabetes Obes Metab. 2020;22(4):699-704. doi:10.1111/dom.13924 · PubMed
  5. Zhong X, Zhao Y, Han M, et al. Effects of Glucagon-Like Peptide-1 Receptor Agonists as Weight Loss Drugs on Pancreatitis and Pancreatic Cancer: A Meta-Analysis. Horm Metab Res. 2026;58(9):354-363. doi:10.1055/a-2923-3830 · PubMed
  6. Benny O, Agarwal A, Alecock H, et al. Dose-response analysis of tirzepatide and acute pancreatitis: An international systematic review and quantitative meta-analysis of randomised trials. Pancreatology. 2026;26(4):552-565. doi:10.1016/j.pan.2026.03.021 · PubMed
  7. WEGOVY (semaglutide) US prescribing information and Medication Guide, sections 5.2, 5.3, 6.1 and 17 (revised 06/2026). DailyMed
  8. ZEPBOUND (tirzepatide) US prescribing information and Patient Information, sections 5.4, 5.5, 6.1 and 17 (revised 08/2026). DailyMed
  9. OZEMPIC (semaglutide) and MOUNJARO (tirzepatide) US prescribing information, sections 5 and 6.1 (checked November 2026). OZEMPIC · MOUNJARO
This article summarises published research for general information. It is not medical advice and does not replace advice from your own care team. Never change a medication or dose without talking to your prescriber.

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