Tirzepatide Safety Profile
Safety information for tirzepatide including common side effects, warnings, and contraindications. Based on the FDA Zepbound prescribing information and published SURPASS and SURMOUNT trial results.
Safety Overview
Tirzepatide has been evaluated in the SURPASS (type 2 diabetes) and SURMOUNT (obesity) phase 3 programmes. The three published trials cited on this page enrolled 475 adults with type 2 diabetes (SURPASS-5, PMID 35133415), 2,539 adults with obesity (SURMOUNT-1, PMID 35658024), and 783 adults in the open-label lead-in of SURMOUNT-4, of whom 670 were randomised (PMID 38078870).
The adverse reaction rates below are taken from the FDA prescribing information rather than from any single trial, because the label pools the placebo-controlled weight-management trials.
Common Adverse Reactions
From Table 2 of the Zepbound prescribing information — reactions occurring in at least 2% of treated adults and more often than placebo, in the placebo-controlled chronic weight management trials:
| Adverse reaction | Placebo (N=958) | 5 mg (N=630) | 10 mg (N=948) | 15 mg (N=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% |
| Dyspepsia | 4% | 9% | 9% | 10% |
| Fatigue | 3% | 5% | 6% | 7% |
Trial-level rates differ from the pooled label figures. SURPASS-5 (PMID 35133415), cited below, reports nausea at 13%–18% and diarrhoea at 12%–21% across tirzepatide arms. Read the label table as the pooled safety population and the trial papers as individual studies; they are not interchangeable.
The label reports gastrointestinal adverse reactions in 56% of treated patients at each strength versus 30% on placebo, and states that “the majority of nausea, vomiting, and/or diarrhea events occurred during dose escalation and decreased over time.” Gastrointestinal reactions led to discontinuation in 1.9%, 3.3%, and 4.3% of the 5 mg, 10 mg, and 15 mg groups, versus 0.5% on placebo. In SURMOUNT-1, adverse events of any type caused discontinuation in 4.3%, 7.1%, and 6.2% of the tirzepatide groups versus 2.6% on placebo.
Serious Warnings
Boxed Warning: Risk of Thyroid C-Cell Tumors
The label’s boxed warning states: “In rats, tirzepatide causes thyroid C-cell tumors. It is unknown whether ZEPBOUND causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined.” This is a rat finding. The label does not claim it has been shown in people.
Other Warnings and Precautions
The current Zepbound label (DailyMed SPL, published 6 May 2026) lists these under Warnings and Precautions, sections 5.2 through 5.10:
- 5.2 Severe gastrointestinal adverse reactions — reported more often on Zepbound (5 mg 1.7%, 10 mg 2.5%, 15 mg 3.1%) than placebo (1%); not recommended in patients with severe gastroparesis
- 5.3 Acute kidney injury due to volume depletion — monitor renal function in patients reporting reactions that could cause volume depletion
- 5.4 Acute gallbladder disease — reported in clinical trials; investigate if cholecystitis is suspected
- 5.5 Acute pancreatitis — reported in clinical trials; discontinue promptly if suspected, and do not restart if confirmed
- 5.6 Hypersensitivity reactions — anaphylaxis and angioedema reported postmarketing
- 5.7 Hypoglycemia — risk increases with concomitant insulin or an insulin secretagogue
- 5.8 Diabetic retinopathy complications in patients with type 2 diabetes — monitor those with a history of retinopathy
- 5.9 Pulmonary aspiration during general anesthesia or deep sedation
- 5.10 Never share a Zepbound KwikPen between patients
Suicidal behavior and ideation is no longer on this label. The label’s own Recent Major Changes table records it as “Suicidal Behavior and Ideation (Removed) 02/2026”. Pages still listing it as a current warning — including earlier versions of this one — are describing a warning the FDA has withdrawn.
Who Should NOT Use Tirzepatide
The label lists two contraindications:
- Personal or family history of medullary thyroid carcinoma, or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Known serious hypersensitivity to tirzepatide or any of the excipients
Special Populations
- Pregnancy: the label states that “weight loss offers no benefit to a pregnant patient and may cause fetal harm,” and advises discontinuing when pregnancy is recognised
- Lactation: there are no data on tirzepatide in animal or human milk, or on effects on the breastfed infant
- Pediatric: safety and effectiveness have not been established under 18 years of age
- Renal impairment: the label recommends no adjustment, including in end-stage renal disease, and reports no change in tirzepatide pharmacokinetics; renal function should still be monitored if reactions could cause volume depletion
- Oral contraceptives: the label warns that tirzepatide may reduce the efficacy of oral hormonal contraceptives because of delayed gastric emptying
This safety information is for educational purposes. Consult prescribing information and healthcare provider.
Sources & Citations
- 2
- 4regulatoryZEPBOUND (tirzepatide) injection, for subcutaneous use — Prescribing Information (DailyMed SPL, published 6 May 2026)
fda-zepbound-label
Disclaimer: This article is for educational purposes only and does not constitute medical advice. The information presented is based on current research but should not be used for diagnosis, treatment, or prevention of any disease. Always consult a qualified healthcare provider before making health decisions.