Zepbound side effects

The most common Zepbound side effects are stomach and bowel problems, led by nausea: 25% to 29% of people in the label trials vs 8% on placebo. Most of it came while the dose was rising and eased over time. Zepbound also carries a boxed warning for thyroid tumors and a short list of serious risks worth knowing before your first shot. Everything below comes from the Zepbound prescribing information (rev. 08/2026). For how Zepbound compares with other GLP-1s and general tips that help, see our GLP-1 side effects guide.

The boxed warning comes first

Zepbound is tirzepatide, a weekly injection. Its label opens with a boxed warning, the FDA’s strongest:

• In rats, tirzepatide caused thyroid C-cell tumors, and the risk rose with dose and time on the drug. Whether it does the same in people is unknown.
• Zepbound is not for anyone with a personal or family history of medullary thyroid carcinoma (MTC) or with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• Tell your clinician if you notice a lump or swelling in your neck, hoarseness, trouble swallowing or shortness of breath.

The label adds that routine calcitonin blood tests or thyroid ultrasounds are of uncertain value for catching MTC early.

Side effects in the label trials, by dose

The main table pools two placebo-controlled trials (Studies 1 and 2 on the label) with 2,519 adults on Zepbound for up to 72 weeks. One of the two trials enrolled people with type 2 diabetes. The table lists effects reported by at least 2% of people on Zepbound and more often than on placebo.

Percent of people with each side effect:

Scroll sideways to see the full table

Source: Zepbound label, Table 1 (placebo n=958; 5 mg n=630; 10 mg n=948; 15 mg n=941).

The useful number is the gap with placebo. At 10 mg, 29% had nausea vs 8% on placebo: about 21 extra people in every 100.

A few patterns stand out. Vomiting rose with dose, from 8% to 13%. Constipation went the other way, from 17% at 5 mg to 11% at 15 mg. Injection-site reactions, such as redness, itching or bruising, affected 6% to 8%.

Side effects led 4.8% of people at 5 mg, 6.3% at 10 mg and 6.7% at 15 mg to stop for good, vs 3.4% on placebo. Most who stopped did so in the first few months, because of stomach side effects.

How the dose ladder affects stomach side effects

Zepbound starts low on purpose. The label’s schedule:

1. 2.5 mg once a week for 4 weeks. This is a starting dose only, not approved as a maintenance dose.
2. 5 mg once a week after that.
3. If needed, increases of 2.5 mg, each after at least 4 weeks on the current dose, up to 15 mg.

The maintenance doses for weight are 5, 10 or 15 mg (10 or 15 mg for sleep apnea). The label says to follow this ladder “to reduce the risk of gastrointestinal adverse reactions”.

The numbers show why. Stomach and bowel side effects of any kind hit 56% of people at every dose, vs 30% on placebo, and most nausea, vomiting and diarrhea happened during dose escalation and decreased over time. Stomach side effects made 1.9% at 5 mg, 3.3% at 10 mg and 4.3% at 15 mg stop treatment, vs 0.5% on placebo.

The label gives your clinician room to adjust. They can weigh how you respond and how you tolerate each step when picking a maintenance dose, and if a maintenance dose is too hard to tolerate, the label says to consider a lower one. Do not skip steps or change your dose yourself. Our general side effects guide covers everyday steps that help with nausea.

If you miss a dose, take it within 4 days (96 hours). After that, skip it and take the next dose on your usual day. Keep at least 3 days (72 hours) between two doses.

Serious risks on the label

These are rarer, but the label lists them as warnings. Rates are from the pooled weight trials.

• Severe stomach problems. Reported by 1.7% at 5 mg, 2.5% at 10 mg and 3.1% at 15 mg, vs 1% on placebo. Zepbound is not recommended for people with severe gastroparesis.
• Kidney injury from dehydration. Acute kidney injury was reported in 0.5% vs 0.2% on placebo. Most cases after approval followed nausea, vomiting or diarrhea.
• Gallbladder disease. Gallstones in 1.1% vs 1%, gallbladder inflammation in 0.7% vs 0.2%, and gallbladder removal in 0.2% vs none on placebo.
• Pancreatitis. Confirmed in 0.2% on Zepbound and 0.2% on placebo in these trials. Cases, some fatal, have been seen with drugs in this class, so stop and get care if you have the warning signs below.
• Serious allergic reactions. Severe reactions occurred in 0.1% vs none on placebo. Anaphylaxis and swelling of the face and throat have been reported since approval.
• Low blood sugar. In the trial of people with type 2 diabetes, 4.2% had low blood sugar vs 1.3% on placebo, and 10.3% of those also taking a sulfonylurea. Your clinician may lower your insulin or sulfonylurea dose.
• Eye changes in type 2 diabetes. Fast improvement in blood sugar can briefly worsen diabetic retinopathy.
• Breathing in stomach contents under anesthesia. Rare cases have been reported with drugs in this class.

Other effects on the label: blood pressure dropped too low in 1.6% vs 0.1% on placebo, more often in people taking blood pressure medicine. Resting heart rate rose by 1 to 3 beats per minute on average. Skin sensitivity (dysesthesia) was rare, at 0.2% to 0.4%.

Never share a Zepbound KwikPen with another person, even with a new needle, because of the risk of passing on infections. The August 2026 label lists its former section on suicidal behavior and ideation as removed in February 2026. Tell your clinician about any change in mood all the same.

Birth control, pregnancy and other medicines

• Birth control pills. Zepbound slows stomach emptying, which can affect pills. The label 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.
• Pregnancy. Zepbound may harm an unborn baby. Stop it when a pregnancy is recognized, and tell your clinician.
• Other pills. Because it slows stomach emptying, Zepbound can change how other oral medicines are absorbed. Drugs with a narrow safe range, such as warfarin, may need closer monitoring.

When to call a doctor

The Medication Guide that comes with Zepbound sets out these signs.

Stop Zepbound and call your clinician right away if you have severe stomach pain that will not go away, with or without vomiting. It may spread to your back. This can be pancreatitis.

Stop Zepbound and get medical help right away for signs of a serious allergic reaction: swelling of the face, lips, tongue or throat, trouble breathing or swallowing, severe rash or itching, fainting or dizziness, or a very fast heartbeat.

Tell your clinician right away if you have:

• Nausea, vomiting or diarrhea that does not go away.
• Pain in your upper stomach, fever, yellow skin or eyes, or clay-colored stools, which can point to gallbladder trouble.

Also tell your clinician about:

• Stomach problems that are severe or do not go away.
• Vision changes, if you have type 2 diabetes.
• Signs of low blood sugar, such as shakiness, sweating, confusion, a fast heartbeat or blurred vision.

If you take too much Zepbound, call your clinician or Poison Help at 1-800-222-1222, or go to the nearest emergency room. You can report side effects to the FDA at 1-800-FDA-1088 or through MedWatch.

A note on compounded tirzepatide

These rates come from trials of Zepbound. Compounded tirzepatide is not Zepbound and not a generic of it. A compounding pharmacy prepares it, it isn’t FDA-approved, and the FDA does not review compounded drugs for safety, effectiveness or quality before they are sold. As of May 31, 2026, the FDA had received more than 730 adverse event reports linked to compounded tirzepatide, and it says the true number is likely higher (FDA). Our compounded tirzepatide vs Zepbound guide sets out the trade-offs.

The bottom line

Zepbound’s side effects are mostly stomach and bowel problems, led by nausea at 25% to 29% vs 8% on placebo, and they cluster while the dose climbs. The slow ladder, starting at 2.5 mg for 4 weeks, exists to keep them down. Read the boxed warning first, know the signs that need a call, and talk to your clinician before changing anything. When you are ready to start, our guide to getting Zepbound online and the Zepbound provider rankings can help.