The Wegovy, Zepbound and Saxenda labels carry a boxed warning for thyroid C-cell tumors seen in rodents, plus warnings for pancreatitis, gallbladder disease, acute kidney injury, hypersensitivity, hypoglycemia and pulmonary aspiration [1][2][3]. In label trials, cholelithiasis occurred in 1.6% of Wegovy injection patients versus 0.7% on placebo, and in 2.2% on Saxenda versus 0.8% [1][3].
Key takeaways
- Wegovy and Zepbound carry a boxed warning because semaglutide and tirzepatide caused thyroid C-cell tumors in rodents; they are contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2 [1][2].
- Gallstones (cholelithiasis) occurred in 1.6% of Wegovy injection patients versus 0.7% on placebo, in 2.2% versus 0.8% on Saxenda, and in 1.1% versus 1% on Zepbound [1][2][3].
- Pancreatitis was confirmed in 0.3% of Saxenda patients versus 0.1% on placebo, and in 0.2% of Zepbound patients versus 0.2% on placebo; labels say to discontinue if it is suspected [1][2][3].
- In a 2-year semaglutide trial in type 2 diabetes, diabetic retinopathy complications occurred in 3% versus 1.8% on placebo [1]; EMA called optic neuropathy (NAION) a very rare side effect of semaglutide, affecting up to 1 in 10,000 people [5].
- Labels tell patients to inform providers before planned surgery because of rare pulmonary aspiration reports, and low blood sugar was 10.3% with a sulfonylurea versus 2.1% without on Zepbound in a type 2 diabetes trial [1][2].
What serious risks do the labels for Wegovy, Zepbound and Saxenda list?
The Wegovy and Zepbound labels open with a boxed warning for thyroid C-cell tumors, and all three labels have a Warnings and Precautions section covering several other serious conditions. The Wegovy label (revised 05/2026) lists acute pancreatitis, acute gallbladder disease, hypoglycemia, acute kidney injury due to volume depletion, severe gastrointestinal reactions, hypersensitivity reactions, diabetic retinopathy complications, heart rate increase and pulmonary aspiration [1].
The Zepbound label (revised 04/2026) lists severe gastrointestinal reactions, acute kidney injury, acute gallbladder disease, acute pancreatitis, hypersensitivity, hypoglycemia, diabetic retinopathy complications, pulmonary aspiration during anesthesia or deep sedation, and a warning not to share a KwikPen between patients [2]. The Saxenda label (revised 02/2026) lists risk of thyroid C-cell tumors, pancreatitis, gallbladder disease, hypoglycemia, heart rate increase, acute kidney injury, severe gastrointestinal reactions, hypersensitivity and pulmonary aspiration [3].
A warning on a label means the event was seen in trials or reported after approval. It does not give any one person's risk, and it does not mean the event is likely. The numbers below come from each label's own trial data, and those trials differ in people, length and design, so the figures should not be compared head to head. Nausea, vomiting and other common side effects are covered in our guide to managing side effects.
This article summarizes labels and regulators. It is not medical advice, and a licensed clinician decides what is right for a person after an evaluation.
What is the boxed warning about thyroid tumors?
The boxed warning says the medicines caused thyroid C-cell tumors in rodents, and it bars their use in people with certain personal or family histories. The Wegovy boxed warning states that "in rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors," and that Wegovy is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [1].
The Zepbound boxed warning describes the same finding in rats given tirzepatide, notes that whether this happens in humans is unknown, and carries the same contraindication [2]. It also states that routine calcitonin monitoring or thyroid ultrasound is of uncertain value for early detection of MTC [2].
The labels tell prescribers to counsel patients about this risk and to inform them of symptoms of thyroid tumors, listed as a mass in the neck, difficulty swallowing (dysphagia), shortness of breath (dyspnea) and persistent hoarseness [1][2]. The Wegovy Medication Guide asks patients to report a lump or swelling in the neck [4].
The Zepbound label states that whether this happens in humans is unknown [2]. The contraindication is a formal safety limit that applies before prescribing [1][2].
How common are gallbladder problems, and what do the labels report?
Gallstones and gallbladder inflammation occurred more often with Wegovy and Saxenda than with placebo in label trials, and the Zepbound label shows a smaller gallstone difference but more gallbladder inflammation. The figures below are the percentages reported in each label's own trials [1][2][3].
Source: [1][2][3] Wegovy (05/2026), Zepbound (04/2026) and Saxenda (02/2026) prescribing information. Each label uses different trials; do not compare bars directly.
| Label | Cholelithiasis (drug vs placebo) | Cholecystitis (drug vs placebo) |
|---|---|---|
| Wegovy injection, adults [1] | 1.6% vs 0.7% | 0.6% vs 0.2% |
| Wegovy tablets, adults [1] | 2.5% vs 1% | Not reported in the label text reviewed |
| Wegovy injection, ages 12 and older [1] | 3.8% vs 0% | 0.8% vs 0% |
| Saxenda, adults [3] | 2.2% vs 0.8% | 0.8% vs 0.4% |
| Zepbound, pooled Studies 1 and 2 [2] | 1.1% vs 1% | 0.7% vs 0.2% |
The Wegovy label states that treatment is associated with an increased occurrence of cholelithiasis and cholecystitis. It adds that substantial or rapid weight loss can increase the risk of cholelithiasis, yet acute gallbladder disease was more common in Wegovy-treated patients than in placebo patients [1]. The Saxenda label notes that most affected patients needed cholecystectomy, and that the excess risk persisted after accounting for the amount of weight loss [3]. In the Zepbound pooled studies, cholecystectomy occurred in 0.2% of tirzepatide patients and none on placebo [2].
If cholelithiasis is suspected, the Wegovy label says gallbladder studies and appropriate clinical follow-up are indicated [1]. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) describes a gallbladder attack as pain in the upper right abdomen, sometimes lasting several hours, and lists symptoms that call for seeing a doctor right away [10].
Can GLP-1 medicines cause pancreatitis, kidney injury or allergic reactions?
Yes, all three have been reported, and the labels treat each as a reason for prompt medical attention. They are uncommon in the trial data, but the labels describe some severe cases [1][2].
Pancreatitis: the Wegovy label says acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed, and that Wegovy should be discontinued if pancreatitis is suspected. In its trials, 4 Wegovy-treated adults (0.2 cases per 100 patient-years) and 1 placebo patient (under 0.1) had confirmed acute pancreatitis [1]. In Saxenda trials, adjudicated pancreatitis occurred in 9 of 3,291 patients (0.3%) versus 2 of 1,843 on placebo (0.1%) [3]. In Zepbound pooled studies it was 0.2% in both groups [2]. NIDDK notes that gallstones are the most common cause of acute pancreatitis [11].
Kidney injury: postmarketing reports include acute kidney injury, in some cases requiring hemodialysis [1][2]. The Zepbound label says these were mostly in patients with gastrointestinal reactions that caused dehydration [2]. The Zepbound label reports acute kidney injury in 0.5% of tirzepatide patients versus 0.2% on placebo [2]. The Wegovy label reports it in 7 adults (0.4 per 100 patient-years) versus 4 on placebo (0.2) [1]. Labels tell clinicians to monitor kidney function in patients reporting reactions that could lead to volume depletion [1].
Hypersensitivity: anaphylaxis and angioedema have been reported after approval. Severe hypersensitivity occurred in 0.1% of Zepbound patients and none on placebo, and the label says to discontinue and seek medical care if it occurs. The drug is not to be used in anyone with a prior serious reaction to it [2].
What eye risks do the labels and regulators describe?
Two separate eye issues exist: diabetic retinopathy complications, which are on the U.S. labels, and a rare optic nerve condition called NAION, which European regulators have added to semaglutide product information. They are different problems and apply to different groups, so they are covered separately.
Diabetic retinopathy. The Wegovy label reports that in a 2-year trial of semaglutide injection in adults with type 2 diabetes and high cardiovascular risk, diabetic retinopathy complications occurred in 3% of semaglutide patients versus 1.8% on placebo. The absolute difference was larger in people with retinopathy at baseline (8.2% vs 5.2%) than in those without it (0.7% vs 0.4%). In a Wegovy trial in adults with type 2 diabetes and a BMI of 27 or more, retinopathy occurred in 4% versus 2.7% [1]. The labels link rapid improvement in glucose control to a temporary worsening of retinopathy and say patients with a history of it should be monitored [1][2]. Zepbound has not been studied in people with proliferative retinopathy or diabetic macular edema [2].
NAION. Non-arteritic anterior ischemic optic neuropathy is an eye condition that can cause vision loss. On June 6, 2025 (revised June 13), the European Medicines Agency's safety committee, PRAC, concluded that NAION is a very rare side effect of semaglutide in Ozempic, Rybelsus and Wegovy, defined as affecting up to 1 in 10,000 people. EMA said large studies in adults with type 2 diabetes suggest about a twofold higher risk than in non-users, roughly one extra case per 10,000 person-years, and told patients to contact a doctor without delay for sudden loss of vision or rapidly worsening eyesight [5]. The Wegovy EU product information states that epidemiological data indicate an increased risk of NAION during semaglutide treatment [6].
In the United States, FDA listed NAION with Ozempic, Rybelsus and Wegovy among its potential signals of serious risks identified through FAERS for October to December 2024, with the status "FDA is evaluating the need for regulatory action" as of March 6, 2025 [7]. The Wegovy U.S. label revised 05/2026 does not list an eye disorder in its postmarketing section, so readers should check current labeling [1].
A Danish and Norwegian registry study of semaglutide in type 2 diabetes found 32 events among semaglutide users and a pooled adjusted hazard ratio of 2.81 (95% CI 1.67 to 4.75), or 1.41 additional events per 10,000 person-years. Its authors noted low event counts, residual confounding, and inconclusive results for obesity use [8].
What should patients know about anesthesia and low blood sugar?
Tell every provider you take a GLP-1 medicine before a planned surgery or procedure, and tell your prescriber if you also take insulin or a sulfonylurea. Both labels address these directly.
Pulmonary aspiration. The Wegovy label reports rare postmarketing cases of pulmonary aspiration in patients receiving GLP-1 receptor agonists and instructs patients to tell their healthcare providers before any planned surgery or procedure [1]. The Zepbound label describes rare reports in patients with residual stomach contents during anesthesia or deep sedation despite fasting [2]. A multi-society clinical guidance, approved by the AGA, ASMBS, ISPCOP and SAGES and affirmed by the ASA Administrative Council, says procedural, anesthesia and prescribing teams should share the decision and assess risk. It notes that patients without elevated risk may continue therapy, a 24-hour liquid diet can be used when delayed stomach emptying is a concern, and, if holding is chosen, the earlier ASA approach is to hold daily forms the day of surgery and weekly forms one week before. The authors say little data exist to build evidence-based guidelines, and the aspiration reports they cite are individual cases [9].
Hypoglycemia. The Wegovy label says it lowers blood glucose and can cause hypoglycemia, and that using it with insulin or an insulin secretagogue may increase the risk. In adults with type 2 diabetes, clinically significant hypoglycemia (under 54 mg/dL) occurred in 6.2% of Wegovy patients versus 2.5% on placebo [1]. In the Zepbound type 2 diabetes study, hypoglycemia occurred in 4.2% versus 1.3% on placebo, and in 10.3% of tirzepatide patients using a sulfonylurea versus 2.1% of those not using one. The label says insulin or secretagogue doses may need to be reduced [2].
Which symptoms need urgent care, according to the labels?
The labels and Medication Guide name specific warning signs. The Wegovy Medication Guide (issued 08/2022; wording may have changed since, so check your current copy) and the prescribing information describe these [4]. This is a summary of label language, not a list for self-diagnosis.
| Concern | Signs named in the materials | What the materials say to do |
|---|---|---|
| Pancreatitis | Severe stomach-area pain that will not go away, which may spread to the back [4]; persistent or severe abdominal pain, sometimes radiating to the back [2] | Stop the drug and call a provider [4]; seek care right away [11] |
| Gallbladder problems | Pain in the upper stomach, fever, yellowing of skin or eyes, clay-colored stools [4] | Call a provider [4]; NIDDK says see a doctor right away for pain lasting several hours, vomiting, fever or chills, jaundice [10] |
| Serious allergic reaction | Swelling of the face, lips, tongue or throat, trouble breathing or swallowing, fainting or dizziness, very rapid heartbeat [4] | Seek medical help [4] |
| Dehydration and kidney problems | Vomiting, diarrhea or nausea that causes dehydration [1][2][4] | Report to a provider; labels call for kidney monitoring [1] |
| Thyroid tumor | Lump or swelling in the neck, trouble swallowing, shortness of breath, persistent hoarseness [1][2][4] | Report to a provider [4] |
| Vision | Sudden loss of vision or rapidly worsening eyesight (EMA, semaglutide) [5]; change in vision in people with type 2 diabetes [4] | Contact a doctor without delay [5] |
| Low blood sugar | Dizziness, sweating, shakiness, confusion [4] | Tell your provider; doses of insulin or a sulfonylurea may need adjusting [1][2] |
What this means in practice
- The Wegovy and Zepbound boxed warnings rest on rodent thyroid findings, and both medicines are contraindicated with a personal or family history of MTC or MEN 2 [1][2].
- Gallstone rates in label trials ranged from 1.1% (Zepbound) to 2.5% (Wegovy tablets), and the trials differ, so the figures cannot rank the drugs [1][2][3].
- Severe or persistent abdominal pain, especially pain that spreads to the back or comes with vomiting or fever, is a reason to call a clinician promptly; labels say to stop the drug if pancreatitis is suspected [1][2][4][11].
- Labels link kidney injury to volume depletion, and the Zepbound label says reported cases were mostly in patients with dehydration from gastrointestinal reactions, so ongoing vomiting or diarrhea deserves attention [1][2].
- Tell any surgeon, endoscopist or anesthesia team that you use a GLP-1 medicine well before a procedure [1][9].
- People with diabetes who take insulin or a sulfonylurea, or who have retinopathy, need individual planning with their prescriber [1][2].
When to talk to a clinician
Raise any of the warning signs above with a clinician promptly, and seek medical help right away for symptoms such as swelling of the face, lips, tongue or throat or trouble breathing or swallowing, as the Medication Guide advises [4]. Mention your history before treatment starts, including gallbladder disease, pancreatitis, thyroid cancer in the family, kidney problems, diabetes, eye disease, and any insulin or sulfonylurea use.
At Healthy Weight Loss 4 U, every program begins with a clinician evaluation, and that evaluation is where to raise the topic of these risks and your own history. A licensed clinician decides whether any treatment is appropriate for you and how you would be monitored. This article is general information and makes no promises about outcomes.
Frequently asked questions
Do GLP-1 medicines cause gallstones?
What is the boxed warning on Wegovy and Zepbound?
Can GLP-1 medicines cause pancreatitis?
What is NAION and is it on the U.S. label?
Should I tell my surgeon I take a GLP-1 medicine?
Is low blood sugar a risk if I do not have diabetes?
Which symptoms mean I should seek care right away?
Sources
- WEGOVY (semaglutide) injection and tablets prescribing information, revised 05/2026. U.S. Food and Drug Administration (Drugs@FDA), 2026. www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s031,218316s00lbl.pdf
- ZEPBOUND (tirzepatide) prescribing information, revised 04/2026. U.S. Food and Drug Administration (Drugs@FDA), 2026. www.accessdata.fda.gov/drugsatfda_docs/label/2026/217806Orig1s050lbl.pdf
- SAXENDA (liraglutide) prescribing information, revised 02/2026. U.S. Food and Drug Administration (Drugs@FDA), 2026. www.accessdata.fda.gov/drugsatfda_docs/label/2026/206321s025lbl.pdf
- WEGOVY Medication Guide (issued 08/2022), included in the 2023 label file. U.S. Food and Drug Administration (Drugs@FDA), 2023. www.accessdata.fda.gov/drugsatfda_docs/label/2023/215256Orig1s006lbl.pdf
- PRAC concludes eye condition NAION is a very rare side effect of semaglutide medicines Ozempic, Rybelsus and Wegovy. European Medicines Agency, 2025. www.ema.europa.eu/en/news/prac-concludes-eye-condition-naion-very-rare-side-effect-semaglutide-medicines-ozempic-rybelsus-wegovy
- Wegovy: EPAR product information (Summary of Product Characteristics). European Medicines Agency, n.d.. www.ema.europa.eu/en/documents/product-information/wegovy-epar-product-information_en.pdf
- October - December 2024: New Safety Information or Potential Signals of Serious Risks Identified by FDA Adverse Event Reporting System. U.S. Food and Drug Administration, 2025. www.fda.gov/drugs/fda-adverse-event-monitoring-system-aems/october-december-2024-new-safety-information-or-potential-signals-serious-risks-identified-fda
- Use of semaglutide and risk of non-arteritic anterior ischaemic optic neuropathy: A Danish-Norwegian cohort study (Simonsen E, et al.). Diabetes, Obesity and Metabolism 27(6):3094-3103, 2025. www.antonpottegaard.dk/publications/originalarticles/o340.pdf
- Multi-society clinical practice guidance for the safe use of glucagon-like peptide-1 receptor agonists in the perioperative period (Kindel TL, Wang AY, Wadhwa A, et al.). Surgical Endoscopy 39:180-183, 2025. link.springer.com/article/10.1007/s00464-024-11263-2
- Symptoms & Causes of Gallstones. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), n.d.. www.niddk.nih.gov/health-information/digestive-diseases/gallstones/symptoms-causes
- Symptoms & Causes of Pancreatitis. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), n.d.. www.niddk.nih.gov/health-information/digestive-diseases/pancreatitis/symptoms-causes
Keep reading
Managing GLP-1 Side Effects: Nausea, Reflux, Red Flags
Read →First 12 Weeks on a GLP-1: What to Expect, Per the Labels
Read →Semaglutide vs Tirzepatide: What the Trials Show
Read →Brand-Name vs Compounded GLP-1 Drugs: What the FDA Says
Read →Questions about your own situation? A clinician can review your history and goals. Related: Personalized Weight Loss Counseling.