In Zepbound's weight-loss trials, 25% to 29% of people had nausea depending on the dose, against 8% on placebo, and stomach and bowel side effects were most frequent while the dose was being increased. Zepbound starts at 2.5 mg a week for four weeks and rises in 2.5 mg steps, at least four weeks apart, to a maintenance dose of 5, 10 or 15 mg. Below is what the FDA label says, with its own numbers.
By Alexandru Vieru | Independently researched | Every number on this page is from the FDA prescribing information on DailyMed. This is general information, not medical advice: your prescriber decides your dose.
Zepbound side effects in its trials
Adults with obesity or overweight in two weight-reduction trials (side effects in 2% or more, and more often than placebo). Percent of people who reported each one:
| Side effect | Placebo (958) | Zepbound 5 mg (630) | Zepbound 10 mg (948) | Zepbound 15 mg (941) |
|---|---|---|---|---|
| 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% |
| Indigestion (dyspepsia) | 4% | 9% | 9% | 10% |
| Injection site reactions | 2% | 6% | 8% | 8% |
| Fatigue | 3% | 5% | 6% | 7% |
| Allergic (hypersensitivity) reactions | 3% | 5% | 5% | 5% |
| Belching | 1% | 4% | 5% | 5% |
| Hair loss | 1% | 5% | 4% | 5% |
| Reflux | 2% | 4% | 4% | 5% |
| Gas | 2% | 3% | 3% | 4% |
| Bloating (abdominal distension) | 2% | 3% | 3% | 4% |
| Dizziness | 2% | 4% | 5% | 4% |
| Low blood pressure | 0% | 1% | 1% | 2% |
How many people stopped because of side effects
In those trials, 4.8%, 6.3% and 6.7% of people on Zepbound 5, 10 and 15 mg stopped because of side effects, against 3.4% on placebo, mostly in the first few months and mostly for stomach and bowel side effects. Those were reported by 56% at every dose and 30% on placebo, and mostly occurred while the dose was being increased.
Serious risks
The label also warns of severe stomach and bowel side effects, kidney injury from dehydration, gallbladder disease, pancreatitis, serious allergic reactions, low blood sugar with insulin or sulfonylureas, diabetic eye complications and inhaling stomach contents under anesthesia. It can make birth control pills less effective: the label advises a non-oral method or a backup method for 4 weeks after starting and after each dose increase.
Boxed warning. Risk of thyroid C-cell tumors: tirzepatide causes these tumors in rats, and it is unknown whether it does in humans. Zepbound must not be used by anyone with a personal or family history of medullary thyroid carcinoma (MTC) or with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
From the FDA prescribing information for Zepbound (revised August 2026), read on DailyMed on 16 October 2026. A summary, not medical advice: a clinician decides whether it suits you.
Zepbound dosage, from the label
The dose schedule
- Starts at 2.5 mg a week for 4 weeks, then rises in 2.5 mg steps at least 4 weeks apart. Maintenance for weight is 5, 10 or 15 mg a week; for sleep apnea, 10 or 15 mg. The maximum is 15 mg a week.
How it’s taken
- Once a week, injected under the skin.
If you miss a dose
Take a missed dose as soon as possible within 4 days (96 hours). After more than 4 days, skip it and take the next dose on your usual day. The weekly day can be changed as long as doses are at least 3 days (72 hours) apart.
From the FDA prescribing information for Zepbound (revised August 2026), read on DailyMed on 16 October 2026. A summary, not medical advice: a clinician decides whether it suits you.
Why 2.5 mg is a starting dose, not a treatment dose
The label uses 2.5 mg only to start; the maintenance doses for weight are 5, 10 or 15 mg a week. A plan priced at the 2.5 mg dose will move up within weeks, so check what your clinic charges at the dose you'll actually stay on.
Does Zepbound make you tired, or cause headaches, anxiety or depression?
The label answers each of these differently, so they are taken one at a time. Every figure here is from the Zepbound prescribing information on DailyMed (revised August 2026), read on 26 October 2026. Tirzepatide is the medicine in Zepbound, so the same answers apply when people ask "does tirzepatide make you tired".
| Question | What the Zepbound label says |
|---|---|
| Tiredness (fatigue) | Listed: 5% on 5 mg, 6% on 10 mg, 7% on 15 mg, against 3% on placebo |
| Headache | Not in the trial table of side effects; named only as a possible sign of low blood sugar |
| Anxiety or mood changes | Not in the trial table; "anxiety, irritability, or mood changes" are named as possible signs of low blood sugar |
| Depression | Not listed as a side effect; a warning on suicidal behavior and ideation was removed from the label in February 2026 |
Fatigue
Yes, tiredness is a listed side effect. In the two weight-reduction trials pooled in the label, fatigue was reported by 5%, 6% and 7% of people on the 5 mg, 10 mg and 15 mg doses, against 3% on placebo. The label's footnote says this row "Includes asthenia, fatigue, lethargy, malaise", so weakness, low energy and generally feeling unwell are counted together. Fatigue is also one of the most common adverse reactions named in the label's highlights, those reported in at least 5% of people.
The label does not say how long fatigue lasts. It does say that most people who stopped Zepbound because of side effects "did so during the first few months of treatment due to gastrointestinal adverse reactions."
Headache
The trial table in the label lists reactions that "occurred more commonly with ZEPBOUND than with placebo and occurred in at least 2% of patients treated with ZEPBOUND." Headache is not on it. The only place the label names headache is the Medication Guide's list of possible signs of low blood sugar (hypoglycemia), next to dizziness, sweating, confusion and shakiness. The label says the risk of low blood sugar "may be higher if you use ZEPBOUND with medicines that can cause low blood sugar, such as an insulin or sulfonylurea." Dizziness itself is in the trial table: 4%, 5% and 4% on the three doses, against 2% on placebo.
Anxiety
Anxiety is not in the trial table either. The Medication Guide names "anxiety, irritability, or mood changes" in the same list of possible signs of low blood sugar. If you feel shaky, anxious or irritable on Zepbound, especially alongside insulin or a sulfonylurea, that list is the reason to mention it to your prescriber.
Depression
The Zepbound label does not list depression as an adverse reaction. Its Recent Major Changes section records "Suicidal Behavior and Ideation (Removed) 02/2026", which means a warning by that name was taken out of the label in February 2026. The label does not explain the removal on the page. Any new or worsening low mood on a medicine is still worth raising with your prescriber, who knows your history.
Zepbound or Mounjaro
Both are tirzepatide from Eli Lilly, with the same weekly doses. Zepbound is approved for weight management and sleep apnea; Mounjaro for type 2 diabetes. Mounjaro's label has its own trial numbers, from people with type 2 diabetes.
What it costs and who prescribes it
For Zepbound's price from the manufacturer, with and without insurance, and the online clinics we review that prescribe it, see our Zepbound guide.
FAQ
How long do Zepbound side effects last? The label says most stopped-for-side-effects cases happened in the first few months, and stomach and bowel side effects mostly while the dose was being increased.
What is the maximum Zepbound dose? 15 mg once a week.
Can I change my Zepbound injection day? Yes, as long as the doses are at least 3 days (72 hours) apart, according to the label.
Source: the Zepbound prescribing information on DailyMed (adverse reactions, dosage and administration, and the boxed warning), read 16 October 2026.
