Zepbound Side Effects: common, serious and how they compare

Key takeaways

• About 56% of adults on Zepbound had a digestive side effect in the weight-loss trials, vs 30% on placebo; nausea affected 25% to 29% depending on dose.^[1]
• Most nausea, vomiting and diarrhea happened during dose increases and decreased over time; 4.8% to 6.7% stopped because of side effects vs 3.4% on placebo.^[1]
• Zepbound may make birth-control pills less effective: the label advises a non-oral or backup method for 4 weeks after starting and after each dose increase.^[1]
• Serious risks include severe digestive reactions, kidney injury from dehydration, gallbladder disease, pancreatitis and allergic reactions; there is a boxed warning about thyroid tumors in rats.^[1]
• In January 2026 the FDA asked for the suicidal-thoughts warning to be removed from Zepbound after finding no increased risk.^[3]

In short: The most common side effects of Zepbound (tirzepatide) are digestive: in the label’s weight-loss trials, about 56% of adults on Zepbound had at least one, compared with 30% on placebo. Nausea affected 25% to 29% depending on the dose (vs 8% on placebo), diarrhea 19% to 23% (vs 8%), constipation 11% to 17% (vs 5%) and vomiting 8% to 13% (vs 2%), mostly while the dose was being increased, and they decreased over time. Serious risks include pancreatitis, gallbladder disease, kidney injury from dehydration and severe allergic reactions, and Zepbound has a boxed warning about thyroid C-cell tumors seen in rats (label checked on 2026-10-06).

This page explains what the official Zepbound prescribing information and Medication Guide say about side effects: how often each one happened at each dose, when they tend to appear and fade, the serious warnings, the birth-control interaction that is specific to tirzepatide, and the symptoms that need urgent care. It is general information, not medical advice. Talk with your prescriber before changing or stopping any medicine.

Where these numbers come from

The main side-effect table on the Zepbound label pools two randomized, double-blind, placebo-controlled trials, the label’s Study 1 (SURMOUNT-1, NCT04184622) and Study 2 (NCT04657003, in adults with type 2 diabetes), with 2,519 adults with obesity or overweight treated for up to 72 weeks; 25% of them had type 2 diabetes. The label adds that side effects in two more weight trials and in the two sleep apnea trials were similar. Zepbound contains tirzepatide, the same medicine as Mounjaro, which is approved for type 2 diabetes; see Mounjaro side effects for that label. Rates from different drugs’ trials cannot be directly compared and may differ in everyday practice.

The most common side effects, by dose

• 5 mg
• 10 mg
• 15 mg
• Placebo

Nausea25%29%28%8%

Diarrhea19%21%23%8%

Constipation17%14%11%5%

Vomiting8%11%13%2%

Abdominal pain9%9%10%5%

Indigestion (dyspepsia)9%9%10%4%

Injection site reactions6%8%8%2%

Fatigue5%6%7%3%

Most common Zepbound side effects by maintenance dose vs placebo

Item	5 mg	10 mg	15 mg	Placebo
Nausea	25%	29%	28%	8%
Diarrhea	19%	21%	23%	8%
Constipation	17%	14%	11%	5%
Vomiting	8%	11%	13%	2%
Abdominal pain	9%	9%	10%	5%
Indigestion (dyspepsia)	9%	9%	10%	4%
Injection site reactions	6%	8%	8%	2%
Fatigue	5%	6%	7%	3%

Studies 1 and 2: 630 people on 5 mg, 948 on 10 mg, 941 on 15 mg, 958 on placebo, up to 72 weeks.

Source: Zepbound prescribing information, Table 1 (checked on October 6, 2026)

Other side effects in at least 2% of people and more often than with placebo were allergic-type (hypersensitivity) reactions (5% at each dose vs 3%), burping (4% to 5% vs 1%), hair loss (4% to 5% vs 1%), acid reflux (4% to 5% vs 2%), gas (3% to 4% vs 2%), bloating (3% to 4% vs 2%), dizziness (4% to 5% vs 2%) and low blood pressure (1% to 2% vs 0%). Note that some effects rise with dose (vomiting, diarrhea) while constipation was most frequent on the lowest dose.

When they tend to happen

According to the label, the majority of nausea, vomiting and diarrhea events occurred during dose escalation and decreased over time, and most people who stopped Zepbound because of side effects did so in the first few months, usually because of digestive effects. The label describes starting at a low dose for 4 weeks and increasing in steps of at least 4 weeks to a maintenance dose; the prescriber decides the pace and the maintenance dose.

Digestive side effects led 1.9%, 3.3% and 4.3% of people on 5, 10 and 15 mg to stop treatment, vs 0.5% on placebo. In a trial that started with an intensive lifestyle program, 10% stopped Zepbound because of side effects vs 2% on placebo. The Medication Guide says to drink fluids to reduce the chance of dehydration and to tell your provider right away about nausea, vomiting or diarrhea that does not go away. Eating approaches people often discuss with their care team are on our GLP-1 diet page.

Birth-control pills: a tirzepatide-specific caution

Serious side effects and warnings

Boxed warning: thyroid C-cell tumors. In a 2-year study in rats, tirzepatide caused thyroid C-cell tumors that increased with dose and duration. It is unknown whether Zepbound causes these tumors, including medullary thyroid carcinoma (MTC), in people. Zepbound must not be used by anyone with a personal or family history of MTC or with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Report a neck lump, hoarseness, trouble swallowing or shortness of breath.

• Severe digestive reactions in 1.7%, 2.5% and 3.1% on 5, 10 and 15 mg vs 1% on placebo. Zepbound is not recommended for people with severe gastroparesis. Ileus, bowel obstruction and severe constipation with fecal impaction have been reported after approval.
• Kidney injury in 0.5% vs 0.2%, often with dehydration; acute kidney failure, sometimes needing dialysis, has been reported after approval.
• Gallbladder disease. Gallstones 1.1% vs 1%, gallbladder inflammation 0.7% vs 0.2%, gallbladder removal 0.2% vs 0%. The label says these events were associated with weight reduction.
• Pancreatitis confirmed in 0.2% on Zepbound and 0.2% on placebo in the weight trials (0.14 vs 0.15 per 100 years of exposure); in the sleep apnea trials, 0.84 per 100 years vs 0. Fatal cases have been reported with this class of medicine.
• Allergic reactions. Immediate reactions (within a day of a dose) in 2.1% vs 0.4%, and severe reactions in 0.1% vs 0%; anaphylaxis and angioedema have been reported after approval. Most trial reactions were skin reactions such as rash or itching.
• Low blood sugar in people with type 2 diabetes: 4.2% vs 1.3%, and 10.3% when combined with a sulfonylurea.
• Diabetic eye complications can temporarily worsen with rapid improvement in blood sugar; people with retinopathy are monitored.
• Aspiration during anesthesia or deep sedation: tell any procedure team you take Zepbound.
• Never share a KwikPen, even with a new needle.

• Zepbound
• Placebo

Low blood sugar, type 2 diabetes trial4.2%1.3%

Non-immediate allergic reactions3.5%2.7%

Immediate allergic reactions2.1%0.4%

Low blood pressure1.6%0.1%

Gallstones1.1%1%

Gallbladder inflammation0.7%0.2%

Kidney injury0.5%0.2%

Gallbladder removal0.2%0%

Less common but important events with Zepbound vs placebo

Item	Zepbound	Placebo
Low blood sugar, type 2 diabetes trial	4.2%	1.3%
Non-immediate allergic reactions	3.5%	2.7%
Immediate allergic reactions	2.1%	0.4%
Low blood pressure	1.6%	0.1%
Gallstones	1.1%	1%
Gallbladder inflammation	0.7%	0.2%
Kidney injury	0.5%	0.2%
Gallbladder removal	0.2%	0%

Pool of Studies 1 and 2 except low blood sugar (Study 2, adults with type 2 diabetes).

Source: Zepbound prescribing information, sections 5 and 6.1 (checked on October 6, 2026)

Other effects people ask about

Hair loss. The label associates it with weight reduction; it was reported in 7.1% of women vs 0.5% of men on Zepbound (placebo 1.3% and 0%), and no one on Zepbound stopped because of it. Injection-site reactions (6% to 8% vs 2%) were more frequent in people who developed antibodies to tirzepatide (11.3% vs 1%). Heart rate rose by 1 to 3 beats per minute on average. Low blood pressure occurred in 1.6% vs 0.1%, more often in people on blood-pressure medicines (2.2%). Less common: dry mouth (1% vs 0.1%), taste changes (0.4% vs 0%) and dysesthesia, unusual skin sensations (0.2% to 0.4% vs 0.1%). Pancreatic enzymes rose on average (amylase 20% to 25%, lipase 28% to 35%); the label says the meaning is unknown without other signs of pancreatitis.

Mood. Zepbound’s label used to carry a suicidal-thoughts warning shared by weight-loss medicines. On January 13, 2026, the FDA said its review of 91 trials with 107,910 participants found no increased risk with GLP-1 medicines and asked for the warning to be removed from Zepbound, Wegovy and Saxenda. Talk to your clinician about any new or worsening depression; in a crisis, call or text 988.

Muscle and appearance. Part of the weight lost on any treatment is lean mass; see muscle loss on GLP-1s, our strength training guide and the protein calculator. Changes in facial fullness after weight loss are discussed in our Ozempic face guide, which applies to any large weight loss.

Who may be at higher risk

• People using birth-control pills (reduced effectiveness after starting and each dose increase).
• People with type 2 diabetes on insulin or sulfonylureas (low blood sugar), or with diabetic retinopathy.
• People on blood-pressure medicines (low blood pressure).
• Anyone who becomes dehydrated, especially with kidney disease.
• People with severe gastroparesis, a history of pancreatitis, or a personal or family history of MTC or MEN 2.
• Anyone scheduled for surgery or deep sedation.

Pregnancy, breastfeeding and other medicines

The label says weight loss offers no benefit to a pregnant patient and may cause fetal harm, and that Zepbound should be stopped when a pregnancy is recognized. A pregnancy registry is available at 1-844-524-0039. In a small single-dose study, tirzepatide was undetectable or very low in breast milk, and its effects on a breastfed infant are unknown. Medicines that need precise blood levels, such as warfarin, may need closer monitoring, and Zepbound should not be combined with other tirzepatide products or GLP-1 medicines.

Compounded tirzepatide

Compounded tirzepatide is not FDA approved. The FDA has reported fraudulent compounded tirzepatide with false pharmacy labels, and adverse events possibly related to compounded doses beyond those in the approved label. Get Zepbound only with a prescription from a state-licensed pharmacy; see our compounded GLP-1 guide.

Reporting side effects, cost and comparisons

Report suspected side effects to Eli Lilly at 1-800-545-5979 or to the FDA at 1-800-FDA-1088 (numbers from the label). On 2026-10-06, Lilly’s self-pay prices for the Zepbound KwikPen were $299 a month for 2.5 mg, $399 for 5 mg and $449 for 7.5 mg to 15 mg (when refilled within 45 days), and people with commercial coverage may pay as little as $25; see the Zepbound cost page and the GLP-1 cost comparison tool. For side effects across the class and against semaglutide, see our GLP-1 side effects guide, Wegovy side effects and Wegovy vs Zepbound.

Questions to ask your doctor or pharmacist

• Which side effects should I expect at my dose, and when should I call you?
• I use birth-control pills: what method should I use when I start and at each dose increase?
• Do my blood-pressure or diabetes medicines need adjusting?
• If side effects are hard to manage, what are our options?
• How should I prepare for surgery or sedation while taking Zepbound?

Frequently asked questions

What are the most common side effects of Zepbound?

Nausea (25% to 29% vs 8% on placebo), diarrhea (19% to 23% vs 8%), constipation (11% to 17% vs 5%), vomiting (8% to 13% vs 2%), stomach pain and indigestion, from the label's weight-loss trials.

Do Zepbound side effects go away?

The label says most nausea, vomiting and diarrhea occurred during dose escalation and decreased over time. Tell your prescriber about side effects that persist or are severe.

Are side effects worse at higher doses?

Some are. Vomiting rose from 8% on 5 mg to 13% on 15 mg, diarrhea from 19% to 23%, and severe digestive reactions from 1.7% to 3.1%. Constipation was actually most frequent on 5 mg.

Does Zepbound affect birth control?

It may make birth-control pills less effective. The label advises switching to a non-oral method or adding a barrier method for 4 weeks after starting and after each dose increase.

Does Zepbound cause hair loss?

Hair loss was reported in 4% to 5% vs 1% on placebo, mostly in women (7.1% vs 0.5% of men). The label links it to weight reduction.

Can Zepbound cause pancreatitis?

Pancreatitis has occurred with tirzepatide and GLP-1 medicines. In the weight trials it was confirmed in 0.2% on Zepbound and 0.2% on placebo. Severe stomach pain that will not go away needs urgent care.

Does Zepbound cause gallbladder problems?

Gallbladder inflammation was reported in 0.7% vs 0.2% on placebo and gallbladder removal in 0.2% vs 0%. The label says gallbladder events were associated with weight reduction.

Is Zepbound linked to depression or suicidal thoughts?

In January 2026 the FDA found no increased risk of suicidal thoughts or behavior with GLP-1 medicines and asked for the warning to be removed from Zepbound. Still report any new or worsening low mood.

Are Zepbound and Mounjaro side effects the same?

Both contain tirzepatide, so the types are the same, but the labels report different rates because the trials differed: Zepbound in people with obesity, Mounjaro in people with type 2 diabetes.

Official sources

• Prescribing information (FDA label)
• FDA approval letter or page
• Manufacturer information

References

1. ZEPBOUND (tirzepatide) injection: prescribing information. Eli Lilly and Company, via DailyMed, 2026. (accessed October 7, 2026) Drug label
2. Jastreboff AM, Aronne LJ, Ahmad NN, et al.. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine, 2022. doi:10.1056/NEJMoa2206038 · PMID 35658024 · NCT04184622 (accessed October 7, 2026) Randomized trial
3. FDA requests removal of suicidal behavior and ideation warning from GLP-1 receptor agonist medications. U.S. Food and Drug Administration, 2026. (accessed October 6, 2026) Government page
4. FDA’s concerns with unapproved GLP-1 drugs used for weight loss. U.S. Food and Drug Administration, 2026. (accessed October 7, 2026) Government page
5. Zepbound coverage and savings. Eli Lilly and Company. (accessed October 6, 2026) Other
6. Drugs@FDA: Zepbound, NDA 217806. U.S. Food and Drug Administration. (accessed October 7, 2026) Government page
7. FDA Approves New Medication for Chronic Weight Management. U.S. Food and Drug Administration, 2023. (accessed October 6, 2026) Government page
8. FDA Approves First Medication for Obstructive Sleep Apnea. U.S. Food and Drug Administration, 2024. (accessed October 7, 2026) Government page
9. Malhotra A, Grunstein RR, Fietze I, et al.. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA). New England Journal of Medicine, 2024. doi:10.1056/NEJMoa2404881 · PMID 38912654 · NCT05412004 (accessed October 6, 2026) Randomized trial
10. Aronne LJ, Sattar N, Horn DB, et al.. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA, 2024. doi:10.1001/jama.2023.24945 · PMID 38078870 · NCT04660643 (accessed October 7, 2026) Randomized trial
11. Aronne LJ, Horn DB, le Roux CW, et al.. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). New England Journal of Medicine, 2025. doi:10.1056/NEJMoa2416394 · PMID 40353578 · NCT05822830 (accessed October 6, 2026) Randomized trial
12. Medicare GLP-1 Bridge: information for providers. Centers for Medicare and Medicaid Services. (accessed October 7, 2026) Government page
13. FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (content current as of 2026-04-01). U.S. Food and Drug Administration. (accessed October 6, 2026) Government page

Facts checked on October 6, 2026

Educational information, not medical advice. Talk with a qualified healthcare professional about your own situation. In an emergency call 911.