Boxed warningIn rats, tirzepatide caused thyroid C-cell tumors; it is unknown whether Zepbound causes these tumors, including medullary thyroid carcinoma (MTC), in people. Zepbound must not be used with a personal or family history of MTC or with MEN 2.[1]
What are Zepbound side effects? Frequency by dose
Zepbound side effects are mainly digestive, and most rise with dose. The label pools the SURMOUNT-1 and SURMOUNT-2 trials (up to 72 weeks) and lists every reaction seen in at least 2% of people and more often than with placebo.[1]
| Side effect | Placebo | 5 mg | 10 mg | 15 mg |
|---|---|---|---|---|
| Nausea | 8% | 25% | 29% | 28% |
| Diarrhea | 8% | 19% | 21% | 23% |
| Vomiting | 2% | 8% | 11% | 13% |
| Constipation | 5% | 17% | 14% | 11% |
| Abdominal pain | 5% | 9% | 9% | 10% |
| Dyspepsia | 4% | 9% | 9% | 10% |
| Injection site reactions | 2% | 6% | 8% | 8% |
| Fatigue | 3% | 5% | 6% | 7% |
| Hypersensitivity reactions | 3% | 5% | 5% | 5% |
| Eructation (burping) | 1% | 4% | 5% | 5% |
| Hair loss | 1% | 5% | 4% | 5% |
| GERD (reflux) | 2% | 4% | 4% | 5% |
| Flatulence | 2% | 3% | 3% | 4% |
| Abdominal distension | 2% | 3% | 3% | 4% |
| Dizziness | 2% | 4% | 5% | 4% |
| Hypotension | 0% | 1% | 1% | 2% |
In the label's definitions, “fatigue” also counts weakness, lethargy and malaise, and “injection site reactions” include bruising, redness, itching, pain and rash at the site.[1]
Side effects of Zepbound in numbers
Stomach side effects were common but rarely severe: 56% of people on each dose had at least one, and 1.7–3.1% had a severe one.[1]
- 56%any GI side effect on each dose (placebo 30%)
- 1.9–4.3%stopped because of GI effects, 5→15 mg (placebo 0.5%)
- 6.7%stopped for any side effect on 15 mg (placebo 3.4%)
The label says the majority of nausea, vomiting and diarrhea “occurred during dose escalation and decreased over time.”[1] In SURMOUNT-1 the stomach side effects were mostly mild to moderate.[2] Timing is covered on how long do Zepbound side effects last.
Which dose has the most side effects?
| Side effect | Placebo | 5 mg | 15 mg | Change 5 → 15 mg |
|---|---|---|---|---|
| Nausea | 8% | 25% | 28% | +3 points |
| Diarrhea | 8% | 19% | 23% | +4 points |
| Vomiting | 2% | 8% | 13% | +5 points |
| Constipation | 5% | 17% | 11% | -6 points |
Vomiting and diarrhea climb with dose; constipation is actually most common at 5 mg. Doses and steps are on the tirzepatide dosage chart.
Zepbound diarrhea, constipation, headache and other symptoms
Each common Zepbound side effect has its own pattern in the label: diarrhea and vomiting rise with dose, constipation falls with dose, and headache was no more common than with placebo.[1][6]
Zepbound diarrhea
Diarrhea affected 19%, 21% and 23% of people on 5, 10 and 15 mg, against 8% on placebo.[1] Together with vomiting it can cause fluid loss, and the label links that loss to acute kidney injury; the Medication Guide asks people to drink fluids and to tell their provider about diarrhea or vomiting that does not stop.[1]
Zepbound constipation
Constipation affected 17% on 5 mg, 14% on 10 mg and 11% on 15 mg, against 5% on placebo, so unlike most side effects it was most common at the lowest dose.[1] Reports after approval added severe constipation with fecal impaction, and intestinal obstruction, to the label.[1]
Zepbound headache
Headache is not a listed Zepbound side effect: in SURMOUNT-1 it was reported by 7.5%, 8.0% and 7.0% of people on 5, 10 and 15 mg, and by 7.3% on placebo.[6] The Medication Guide mentions headache only as a possible sign of low blood sugar, a risk mainly for people also taking insulin or a sulfonylurea.[1]
Zepbound fatigue
Fatigue affected 5%, 6% and 7% of people on 5, 10 and 15 mg, against 3% on placebo; the label's term also counts weakness, lethargy and malaise.[1] Dizziness (4–5% vs 2%) and low blood pressure (1–2% vs 0%) were also more common, and the label ties low blood pressure partly to fluid loss.[1]
Zepbound sulfur burps and burping
Burping, which the label calls eructation, affected 4–5% of people on Zepbound versus 1% on placebo.[1] The label records burping but does not describe its smell, so “sulfur burps” is a user term rather than a label finding. Gas (3–4% vs 2%), bloating (3–4% vs 2%), indigestion (9–10% vs 4%) and reflux (4–5% vs 2%) are listed alongside it.[1]
Other common side effects
- Nausea (25–29% vs 8%) and vomiting (8–13% vs 2%): most frequent in the weeks after each dose increase, then less common.[1]
- Stomach pain (9–10% vs 5%): the label's term covers discomfort, tenderness and lower or upper abdominal pain. Severe pain that does not go away is a pancreatitis warning sign.[1]
- Injection-site reactions (6–8% vs 2%): bruising, redness, itching, pain or rash; see Zepbound injection sites.
- Hair loss (4–5% vs 1%): linked to weight reduction and more common in women.[1]
Drinking alcohol is not addressed in the label; what the label and NIH sources do say is on Zepbound and alcohol.
Serious side effects and when to call a doctor
The Zepbound Medication Guide names the symptoms that need prompt medical attention; the table summarizes them.[1]
| Problem | Symptoms the guide lists | What it says to do |
|---|---|---|
| Pancreatitis | Severe stomach pain that will not go away, with or without vomiting; may spread to the back | Stop Zepbound and call your provider right away |
| Serious allergic reaction | Swelling of face, lips, tongue or throat; trouble breathing or swallowing; severe rash or itching; fainting; very fast heartbeat | Stop Zepbound and get medical help right away |
| Gallbladder problems | Upper stomach pain, fever, yellow skin or eyes, clay-colored stools | Tell your provider right away |
| Dehydration and kidney problems | Nausea, vomiting or diarrhea that does not go away | Tell your provider right away; drink fluids |
| Severe stomach problems | Stomach problems that are severe or do not go away | Tell your provider |
| Possible thyroid tumor | Lump or swelling in the neck, hoarseness, trouble swallowing, shortness of breath | Tell your provider |
| Low blood sugar (with insulin or a sulfonylurea) | Dizziness, sweating, confusion, shakiness, fast heartbeat, hunger | Talk to your provider about managing it |
| Surgery or sedation | Risk of food getting into the lungs | Tell every provider you take Zepbound before a procedure |
| Sudden vision loss in one eye (NAION; FDA warning added November 2026)[7] | Painless decreased, blurred or missing vision in one eye, or color changes | Contact a health care professional right away |
What if you take too much Zepbound?
For an overdose, the label says to contact the Poison Help Line (1-800-222-1222) or a medical toxicologist. Treatment is supportive, and observation may be needed for some time because tirzepatide's half-life is about 5 days.[1]
Weight regain after stopping Zepbound
Stopping Zepbound is followed by weight regain on average: in SURMOUNT-4, people switched to placebo after 36 weeks on tirzepatide regained 14.0% of body weight over the next year, while those who continued lost a further 5.5%.[4] The label does not list withdrawal symptoms.[1] Results by dose are on tirzepatide for weight loss.
Zepbound side effects: thyroid and cancer warning
The thyroid warning comes from animal studies; whether Zepbound causes thyroid cancer in people is not known. In rats, tirzepatide caused dose- and duration-dependent thyroid C-cell tumors. The label contraindicates Zepbound for anyone with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia type 2 (MEN 2).[1]
Other warnings and precautions in the label: severe stomach reactions (not recommended in severe gastroparesis), acute kidney injury from dehydration, acute gallbladder disease, acute pancreatitis, serious allergic reactions, low blood sugar with insulin or sulfonylureas, worsening diabetic eye disease in type 2 diabetes, pulmonary aspiration under anesthesia, and never sharing a KwikPen.[1] A warning on suicidal thoughts was removed from the label in February 2026.[5] On November 9, 2026, the FDA required all GLP-1 drug labels, Zepbound included, to add a warning about NAION, a rare eye condition that can cause sudden vision loss; in the FDA's trial analysis it occurred at 6.4 versus 3.8 cases per 100,000 person-years. More on tirzepatide side effects.[7]
Other measured effects
Several smaller effects were measured in the same trials and appear in the label text rather than the main table.[1]
- Heart rate: up by 1 to 3 beats per minute on average.
- Hair loss: 7.1% of women vs 0.5% of men; see Zepbound side effects in females.
- Gallstones: 1.1% vs 1% on placebo; cholecystitis 0.7% vs 0.2%.
- Pancreatitis (adjudicated): 0.2% vs 0.2%.
- Allergic reactions within a day of a dose: 2.1% vs 0.4% on placebo.
Side effects in the sleep apnea and long-term trials
The other Zepbound trials found the same kinds of side effects. In the sleep apnea trials (SURMOUNT-OSA) they were similar to the weight trials; in SURMOUNT-3, 10% stopped because of side effects versus 2% on placebo; and 7% stopped during the 36-week lead-in of SURMOUNT-4.[1][3][4] SURMOUNT-1 itself reported 4.3%, 7.1% and 6.2% stopping for adverse events on 5, 10 and 15 mg versus 2.6% on placebo.[2]
For the same molecule across Mounjaro and Zepbound, including fatigue, see tirzepatide side effects.
Related
- How long side effects lastWeek-by-week timeline
- Side effects in femalesHair loss, birth control, pregnancy
- Zepbound injection sitesWhere to inject and site reactions
Frequently asked questions
What are the most common Zepbound side effects?
Nausea, diarrhea, vomiting and constipation. Nausea affected 25%, 29% and 28% of people on 5, 10 and 15 mg, versus 8% on placebo.[1]
What are the serious side effects of Zepbound?
The label lists pancreatitis, gallbladder disease, kidney injury from dehydration, serious allergic reactions, low blood sugar with insulin or sulfonylureas, and a boxed warning about thyroid tumors seen in rats.[1]
Does Zepbound cause thyroid cancer?
It is not known. Tirzepatide caused thyroid C-cell tumors in rats; human risk is unknown, and people with a personal or family history of medullary thyroid carcinoma or MEN 2 must not use it.[1]
Do Zepbound side effects go away?
Most nausea, vomiting and diarrhea occurred during dose increases and decreased over time in the trials.[1]
Does Zepbound cause headaches?
Does Zepbound cause diarrhea or constipation?
Both: diarrhea affected 19–23% and constipation 11–17% of people on 5–15 mg, against 8% and 5% on placebo. Diarrhea rose with dose; constipation was highest at 5 mg.[1]
Can Zepbound cause muscle pain?
Muscle pain is not one of the reactions in the label's table of side effects seen in at least 2% of people and more often than with placebo.[1] Tell your provider about any new symptom.
When should I call a doctor about Zepbound side effects?
Right away for severe stomach pain that does not go away, signs of a serious allergic reaction, upper stomach pain with fever or yellow skin, or vomiting and diarrhea that do not stop.[1]
Sources
- Zepbound (tirzepatide) injection: prescribing information, Medication Guide and Instructions for Use
- Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1)
- Malhotra A et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA)
- Aronne LJ et al. Continued treatment with tirzepatide for maintenance of weight reduction (SURMOUNT-4)
- Drugs@FDA: NDA 217806 (Zepbound) approval history and supplement letters
- NCT04184622 (SURMOUNT-1) posted results: outcome measures and adverse events
- FDA requires safety labeling changes for GLP-1 receptor agonists due to potential increased risk of rare but serious eye condition (NAION)