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The most common Zepbound side effects are nausea, diarrhea, vomiting, constipation, stomach pain and indigestion, and they happen mostly while the dose is being raised. That is the picture in the current U.S. prescribing information for Zepbound (tirzepatide), revised in August 2026. The label also lists injection site reactions, fatigue, allergic (hypersensitivity) reactions, belching, hair loss and heartburn in at least 5% of users, and it carries a boxed warning about thyroid C-cell tumors. This guide goes through the Zepbound label section by section: how side effects changed with the dose, what the sleep apnea trials found, the less common reactions and lab changes, and the serious warnings.
Peptide Labs does not sell Zepbound or any prescription drug. For a shorter comparison of Zepbound with Mounjaro, the diabetes brand of the same drug, see our overview of tirzepatide side effects.
Key Takeaways
- Nausea affected 25% to 29% of adults across Zepbound's three maintenance doses, versus 8% on placebo.
- Vomiting and severe digestive reactions became more frequent at higher doses; constipation did not.
- In the sleep apnea trials, side effects were similar to the weight-management trials.
- Zepbound can make birth control pills less effective for a period after starting and after each dose increase.
- The FDA had the suicidal-thoughts warning removed; the label recorded the change in February 2026.
Most common Zepbound side effects, by dose
The label’s main table pools two 72-week trials of 2,519 adults with obesity or overweight, with or without type 2 diabetes. Their average age was 47 and 37% were men. Zepbound has three maintenance doses, shown here as lowest, middle and highest. The table lists reactions that occurred in at least 2% of people on Zepbound and more often than on placebo.
| Side effect | Placebo | Lowest dose | Middle dose | Highest dose |
|---|---|---|---|---|
| Nausea | 8% | 25% | 29% | 28% |
| Diarrhea | 8% | 19% | 21% | 23% |
| Vomiting | 2% | 8% | 11% | 13% |
| Constipation | 5% | 17% | 14% | 11% |
| Stomach pain | 5% | 9% | 9% | 10% |
| Indigestion | 4% | 9% | 9% | 10% |
| Injection site reactions | 2% | 6% | 8% | 8% |
| Fatigue | 3% | 5% | 6% | 7% |
| Allergic reactions (mostly skin) | 3% | 5% | 5% | 5% |
| Belching | 1% | 4% | 5% | 5% |
| Hair loss | 1% | 5% | 4% | 5% |
| Heartburn (GERD) | 2% | 4% | 4% | 5% |
| Gas and bloating | 2% each | 3% each | 3% each | 4% each |
| Dizziness | 2% | 4% | 5% | 4% |
| Low blood pressure | 0% | 1% | 1% | 2% |
How side effects changed with the dose
Digestive side effects affected 56% of people at every Zepbound dose, versus 30% on placebo, and the label says most nausea, vomiting and diarrhea happened during dose increases and eased over time. The dose made more difference to how bad they got:
- Severe digestive reactions: 1.7%, 2.5% and 3.1% from the lowest to the highest dose, versus 1% on placebo.
- Stopping because of digestive side effects: 1.9%, 3.3% and 4.3%, versus 0.5%.
- Stopping because of any side effect: 4.8%, 6.3% and 6.7%, versus 3.4%, mostly in the first few months.
Two later trials give a wider view. In a trial that began with an intensive lifestyle program, 10% of people on Zepbound stopped because of side effects, versus 2% on placebo. In a withdrawal trial, 7% stopped during the first 36 weeks, before anyone was switched to placebo.
Side effects in the sleep apnea trials
Zepbound is also approved for moderate to severe obstructive sleep apnea in adults with obesity. The approval rests on two 52-week trials, together called SURMOUNT-OSA, in 467 adults: one in people not using a CPAP-type machine and one in people who were. The label says side effects were similar to the weight-management trials. The published results in the New England Journal of Medicine, funded by Eli Lilly, give these figures:
| Adverse event | No-PAP trial: tirzepatide | No-PAP trial: placebo | PAP trial: tirzepatide | PAP trial: placebo |
|---|---|---|---|---|
| Diarrhea | 26.3% | 12.5% | 21.8% | 8.8% |
| Nausea | 25.4% | 10.0% | 21.8% | 5.3% |
| Vomiting | 17.5% | 4.2% | 9.2% | 0.9% |
| Constipation | 15.8% | 2.5% | 15.1% | 4.4% |
| Serious adverse events | 7.9% | 5.8% | 5.9% | 10.5% |
| Stopped because of adverse events | 4.4% | 1.7% | 3.4% | 7.0% |
Digestive events were mostly mild to moderate and most frequent during dose escalation. Two cases of acute pancreatitis were confirmed in the tirzepatide group of the PAP trial, and the label reports a higher exposure-adjusted pancreatitis rate in the sleep apnea trials than on placebo, which had none. Each group had only about 115 to 120 people, so these percentages are less precise than the weight-trial figures.
Less common reactions and lab changes
Further down, the label reports reactions that are easy to miss in a summary:
- Low blood pressure: 1.6% versus 0.1%, more often in people taking blood pressure medicines (2.2%) and sometimes linked to dehydration.
- Heart rate: an average rise of 1 to 3 beats per minute.
- Taste and mouth: altered taste in 0.4% versus none, and dry mouth or throat in 1% versus 0.1%.
- Altered skin sensation (dysesthesia): 0.2% to 0.4%, versus 0.1%.
- Hair loss: linked to weight reduction and far more common in women (7.1%) than men (0.5%); no one on Zepbound stopped because of it.
- Antibodies: 64.5% of people in the weight trials developed antibodies to tirzepatide. Allergic reactions occurred in 6.2% of those with antibodies versus 3% without, and injection site reactions in 11.3% versus 1%.
- Pancreatic enzymes: average amylase rose 20% to 25% and lipase 28% to 35%. The label says the meaning of these rises without pancreatitis symptoms is unknown.
Serious warnings on the Zepbound label
The boxed warning says tirzepatide caused thyroid C-cell tumors in rats, and it is unknown whether it does in humans. Zepbound is not for people with a personal or family history of medullary thyroid carcinoma or with MEN 2. The other warnings are:
- Severe digestive reactions; Zepbound is not recommended in severe gastroparesis.
- Acute kidney injury from dehydration: 0.5% versus 0.2% in the weight trials.
- Gallbladder disease: gallstones 1.1% versus 1%, gallbladder inflammation 0.7% versus 0.2%, and gallbladder removal 0.2% versus none.
- Pancreatitis: 0.2% in both groups in the weight trials; fatal and non-fatal severe forms have been reported.
- Serious allergic reactions: severe reactions in 0.1% versus none.
- Low blood sugar: in a trial of adults with type 2 diabetes, 4.2% versus 1.3%, rising to 10.3% in people also taking a sulfonylurea.
- Diabetic eye disease: the section revised in August 2026 says rapid improvement in blood sugar has been linked to temporary worsening of diabetic retinopathy, so people with a history of it should be monitored.
- Anesthesia: rare reports of stomach contents entering the lungs during surgery or deep sedation; tell the care team beforehand.
Post-approval reports add bowel obstruction, ileus and severe constipation, including fecal impaction, as well as kidney failure sometimes needing dialysis.
Birth control, pregnancy and breastfeeding
Zepbound slows stomach emptying, which can reduce how well birth control pills are absorbed. The effect is largest after the first dose and fades over time. In a study with a single dose, peak levels of the pill’s hormones fell by 55% to 66%. The label therefore advises switching to a non-oral method, or adding a barrier method, for 4 weeks after starting and for 4 weeks after each dose increase. Zepbound should be stopped when pregnancy is recognized, and a pregnancy registry collects outcomes. In a small lactation study of 11 women, tirzepatide was undetectable in most breast milk samples, but there are no data on effects in breastfed infants.
Vials, pens and 2026 label changes
Zepbound now comes as single-dose pens, single-dose vials, multi-dose vials and a multi-dose KwikPen. The side effect data apply to all of them because the drug is the same. The KwikPen carries its own warning, added in January 2026: never share it, even with a new needle, because of the risk of passing on blood-borne infections. The severe digestive reactions section was updated in February 2026 and the retinopathy section in August 2026. The suicidal behavior warning was removed after the FDA’s January 13, 2026 review found no increased risk, although the FDA still advises reporting new or worsening depression or mood changes. For how tirzepatide compares with semaglutide, see semaglutide vs tirzepatide and our Wegovy side effects guide; our tirzepatide profile covers the molecule itself.
Frequently Asked Questions
What are the most common side effects of Zepbound?
Nausea, diarrhea, vomiting, constipation, stomach pain and indigestion. Nausea affected 25% to 29% of adults on Zepbound in the weight trials, versus 8% on placebo.
Do Zepbound side effects get worse at higher doses?
Vomiting, severe digestive reactions and stopping because of side effects rose with the dose. Nausea was similar across doses, and constipation was actually less common at the highest dose.
Are Zepbound side effects different for sleep apnea?
The label says side effects in the sleep apnea trials were similar to those in the weight trials. Diarrhea and nausea each affected about 22% to 26% of people on tirzepatide.
Does Zepbound raise heart rate?
Slightly. The label reports an average increase of 1 to 3 beats per minute compared with placebo.
Does Zepbound affect birth control pills?
It can. The label advises switching to a non-oral method or adding a barrier method for 4 weeks after starting and after each dose increase.
Are the vial and pen side effects the same?
Yes. They contain the same drug, so the label’s side effect data apply to every presentation. The multi-dose KwikPen must never be shared.
This article is general information, not medical advice. Peptide Labs does not sell prescription drugs, including any product named here. Read the Medication Guide that comes with a prescription, and ask a pharmacist or prescriber how this information applies to you.
Last reviewed September 2026.
Related guides: GLP-1 Hair Loss: How Common It Is and What Causes It, Ozempic Face: What It Is and What the Evidence Says, GLP-1 Side Effects: What Every GLP-1 Drug Label Warns About, Zepbound Sleep Apnea Approval: What SURMOUNT-OSA Found.