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Side effects

Zepbound side effects

Zepbound side effects in the FDA label are led by digestive effects, reported by 56% of patients at each dose in the 72-week weight trials, against 30% on placebo.1 The label carries a boxed warning for thyroid C-cell tumors seen in rats.2 It also warns of pancreatitis, gallbladder disease, kidney injury and serious allergic reactions.3

This page summarizes published sources for information only. It is not medical advice and does not tell anyone to use a product. Questions about your own health belong with a licensed clinician. For questions about an order or a product, contact us.

Where these numbers come from

Most rates here come from Table 1 of the Zepbound label, which pools two 72-week weight trials of 5 mg, 10 mg and 15 mg once weekly against placebo, in adults with or without type 2 diabetes.1 Side effects in the two 52-week sleep apnea trials were similar.1

Most common side effects

Side effect 5 mg 10 mg 15 mg Placebo
Nausea1 25% 29% 28% 8%
Diarrhea1 19% 21% 23% 8%
Constipation1 17% 14% 11% 5%
Vomiting1 8% 11% 13% 2%
Stomach pain or discomfort1 9% 9% 10% 5%
Indigestion (dyspepsia)1 9% 9% 10% 4%
Injection site reactions1 6% 8% 8% 2%
Fatigue, weakness, lethargy or malaise1 5% 6% 7% 3%
Allergic reactions, mostly rash or itching1 5% 5% 5% 3%
Hair loss1 5% 4% 5% 1%
Belching1 4% 5% 5% 1%
Acid reflux (GERD)1 4% 4% 5% 2%
Dizziness1 4% 5% 4% 2%
Gas1 3% 3% 4% 2%
Bloating1 3% 3% 4% 2%

Most nausea, vomiting and diarrhea began while the dose was being raised and became less frequent over time.1 Severe digestive side effects affected 1.7% of patients on 5 mg, 2.5% on 10 mg and 3.1% on 15 mg, against 1% on placebo.3

Side effects led 4.8%, 6.3% and 6.7% of patients on the three doses to stop treatment, against 3.4% on placebo.1 Digestive reasons alone accounted for 1.9%, 3.3% and 4.3%, against 0.5%, mostly in the first few months.1

Injection site reactions included bruising, redness, itching, pain and rash.1 They were more common in people who developed antibodies to tirzepatide, at 11.3% against 1%.1

Less common effects and lab changes

  • Low blood pressure: 1.6% against 0.1% on placebo.1 On Zepbound it was more frequent in people also taking blood pressure medicines (2.2%) than in those who were not (1.2%), and it also occurred with digestive side effects and dehydration.1
  • Gallbladder events: gallstones in 1.1% against 1%, gallbladder inflammation in 0.7% against 0.2%, and gallbladder removal in 0.2% against 0%.31
  • Acute kidney injury: 0.5% against 0.2%.1
  • Low blood sugar (below 54 mg/dL): 0.3% against 0% in the trial of adults without diabetes, which did not track it systematically.1 In the type 2 diabetes trial it was 4.2% against 1.3%, and 10.3% in people also taking a sulfonylurea, against 2.1% in those who were not.31
  • Heart rate: heart rate rose by an average of 1 to 3 beats per minute, with no rise on placebo.1
  • Mouth and taste: dry mouth or throat in 1% against 0.1%, and altered taste (dysgeusia) in 0.4% against 0%.1
  • Abnormal skin sensations (dysesthesia): 0.2% to 0.4% against 0.1%.1
  • Pancreatic enzymes: amylase rose 20% to 25% and lipase 28% to 35%, against 2.1% and 5.8% on placebo.1 Without pancreatitis symptoms, the meaning of these rises is unknown.1
  • Antibodies: 64.5% of patients in the weight trials and 60.6% in the sleep apnea trials developed antibodies to tirzepatide.1 No clinically significant effect of these antibodies on drug levels or effectiveness has been identified.1
  • Severe allergic reactions: 0.1% against 0%.3

Warnings in the label

Boxed warning: thyroid C-cell tumors

In rats, tirzepatide caused thyroid C-cell tumors that increased with dose and with length of treatment, at exposures relevant to people.2 Whether it causes these tumors in humans is unknown.2 The label notes that routine calcitonin tests or thyroid ultrasound are of uncertain value for catching this cancer early.2

Other warnings

  • Severe digestive problems: Zepbound is not recommended for people with severe gastroparesis, meaning very slow stomach emptying.3
  • Dehydration and kidney injury: nausea, vomiting or diarrhea can cause dehydration, which may lead to kidney problems.10 Acute kidney injury, sometimes needing dialysis, has been reported since approval, mostly in people with these digestive side effects.3 The label calls for kidney checks in people with these symptoms, especially when starting or raising the dose.310
  • Gallbladder disease: signs include upper stomach pain, fever, yellow skin or eyes, and clay-colored stools.310
  • Pancreatitis: severe stomach pain that will not go away, sometimes reaching the back, with or without nausea or vomiting, is a reason to stop Zepbound and get care.310
  • Serious allergic reactions: signs include swelling of the face, lips, tongue or throat, trouble breathing or swallowing, fainting, a very fast heartbeat or a severe rash.310
  • Low blood sugar: the risk is higher with insulin or a sulfonylurea.3 Signs include dizziness, sweating, shakiness, confusion, hunger, headache and a fast heartbeat.310
  • Diabetic retinopathy: people with type 2 diabetes and a history of retinopathy should be monitored, because temporary worsening has been reported with rapid improvement in blood sugar.311
  • Pills taken by mouth: slower stomach emptying can change how oral medicines are absorbed, so drugs that need exact blood levels, such as warfarin, need monitoring.12

Reported after approval

These reports are voluntary, so their frequency and whether the drug caused them cannot always be judged.9 They include acute pancreatitis (hemorrhagic and necrotizing forms, sometimes fatal), ileus, intestinal obstruction, severe constipation including fecal impaction, anaphylaxis, angioedema, and acute kidney failure or worsening of chronic kidney failure, sometimes needing dialysis.9 Pulmonary aspiration during anesthesia has been reported with GLP-1 receptor agonists.9

Who should not use Zepbound, and special groups

  • Contraindications: a personal or family history of medullary thyroid carcinoma or MEN 2, or a known serious allergy to tirzepatide or any ingredient.5
  • Pregnancy: weight loss offers no benefit during pregnancy and Zepbound may cause fetal harm, so it is stopped when pregnancy is recognized.13
  • Breastfeeding: in 11 women given one 5 mg dose, tirzepatide was undetectable in 164 of 171 breast milk samples.13 No data are available on effects on breastfed infants or on milk production.13
  • Birth control pills: they may work less well on Zepbound; the label's backup advice is in Zepbound dosage.12
  • Age: safety and effectiveness are not established in pediatric patients.13 Adults 65 and older, 9% of weight-trial patients, showed no overall differences in safety or effectiveness.13
  • Other GLP-1 medicines: the label does not recommend using Zepbound with any other tirzepatide product or any GLP-1 receptor agonist.14

Forms and storage are on What is Zepbound?, and trial results are in Zepbound benefits and uses. For the same drug in diabetes, see Mounjaro side effects; for the drug class, see GLP-1 side effects.

More on Zepbound

  • Zepbound dosage

    Published dosing information for Zepbound from labels and studies, with its source, and why it is not advice for you.

  • Zepbound benefits and uses

    What published sources report about Zepbound and its uses, with the evidence level of each finding. No promises.

Frequently asked questions

Is Zepbound safe to take?

Zepbound is FDA-approved, and its label sets out the known risks.43 The most common side effects are digestive, such as nausea, diarrhea, vomiting and constipation.1 A boxed warning covers thyroid C-cell tumors seen in rats, and people with a personal or family history of medullary thyroid carcinoma or MEN 2 must not use it.25 Because it is prescription-only, a prescriber decides whether it suits a given patient.6

Does Zepbound cause hair loss?

Hair loss was reported by 4% to 5% of patients on Zepbound in the 72-week weight trials, against 1% on placebo.1 The label says hair loss on Zepbound was associated with weight reduction.7 It was far more common in women, at 7.1%, than in men, at 0.5%.7 No patient treated with Zepbound stopped treatment because of hair loss.7

Does Zepbound cause thyroid cancer?

Tirzepatide caused thyroid C-cell tumors in rats, but whether Zepbound causes these tumors in humans, including medullary thyroid carcinoma (MTC), is unknown.2 People with a personal or family history of MTC, or with MEN 2, must not use it.5 The label asks patients to report a neck lump, trouble swallowing, shortness of breath or hoarseness that does not go away.2

Does Zepbound cause suicidal thoughts?

The current label has no warning about suicidal behavior or thoughts.8 FDA began evaluating a possible signal of suicidal ideation across GLP-1 receptor agonists in July 2023.8 On January 13, 2026, FDA asked Lilly to remove the suicidal behavior and ideation warning from the Zepbound label, and it approved that change on February 25, 2026.8

Do I need to stop Zepbound before surgery?

The label does not set a pause before surgery, and it says there are not enough data to show whether stopping Zepbound lowers the risk.3 Zepbound slows stomach emptying, and rare cases of food or liquid entering the lungs under general anesthesia or deep sedation have been reported with GLP-1 receptor agonists.3 The label asks patients to tell every provider about Zepbound before a planned procedure.3

Does Zepbound cause pancreatitis?

In the weight trials, acute pancreatitis confirmed by adjudication occurred in 0.2% of patients on Zepbound and 0.2% on placebo.1 In the two sleep apnea trials, the rate was 0.84 patients per 100 years of exposure on Zepbound, against 0 on placebo.1 The label warns that acute pancreatitis, including fatal cases, has been seen with GLP-1 receptor agonists or Zepbound.3 Fatal hemorrhagic or necrotizing cases have also been reported since approval.9

Written by D2C Peptides Editorial Team.

Pending qualified review.

Updated .

Sources

  1. Zepbound Prescribing Information, revised 08/2026: Section 6.1 Clinical Trials Experience (Table 1 and text). Eli Lilly and Company; posted by U.S. Food and Drug Administration, 2026.
  2. Same source as 1: Boxed Warning, Risk of Thyroid C-Cell Tumors.
  3. Same source as 1: Sections 5.2 to 5.10 Warnings and Precautions.
  4. FDA Approves New Medication for Chronic Weight Management (news release, November 8, 2023). U.S. Food and Drug Administration, 2023.
  5. Same source as 1: Section 4 Contraindications and Section 5.1.
  6. Drugs@FDA: NDA 217806, Zepbound (tirzepatide) application overview. U.S. Food and Drug Administration, 2026.
  7. Same source as 1: Section 6.1, Hair Loss.
  8. FDA supplement approval letter, NDA 217806/S-042 (safety labeling changes), signed February 25, 2026. U.S. Food and Drug Administration, 2026.
  9. Same source as 1: Section 6.2 Postmarketing Experience.
  10. Same source as 1: Zepbound Medication Guide, revised 04/2026 (in the 08/2026 label file).
  11. FDA corrected supplement approval letter, NDA 217806/S-041 (SURPASS-CVOT labeling), action date August 26, 2026. U.S. Food and Drug Administration, 2026.
  12. Same source as 1: Section 7 Drug Interactions and Section 8.3 Contraception.
  13. Same source as 1: Section 8 Use in Specific Populations (pregnancy, lactation, pediatric, geriatric, renal, hepatic).
  14. Same source as 1: revised 08/2026 (NDA 217806/S-041): Section 1 Indications and Usage.