Why can Zepbound cause headaches and what to do about it?
Zepbound (tirzepatide) might sometimes cause headaches, but this side effect is usually mild and manageable for most people. Headaches are not listed as a common side effect in the FDA-approved labeling for Zepbound, but have been reported in other studies. Below, we will review why Zepbound can cause headaches and how to manage them.
Why Zepbound Can Cause Headaches
Although headaches were not a commonly-reported side effect during Zepbound clinical trials, a 2023 systematic review and meta-analysis found that headaches were reported by about 4-5% of patients taking the medication in other studies. There are also case reports of patients taking Zepbound who developed headaches during treatment. The incidence of headache appears to increase with higher doses.
There are several reasons why Zepbound might trigger headaches in some individuals:
- Dehydration: Zepbound often reduces appetite and can cause gastrointestinal side effects like nausea or vomiting, both of which may lead to lower fluid intake or increased fluid loss.
- Blood Sugar Fluctuations: Since tirzepatide can lower blood glucose, rapid changes in blood sugar levels can result in headaches, particularly during periods of dose adjustment or missed meals.
- Electrolyte Imbalances: Vomiting and diarrhea, which are possible side effects, can disturb the balance of electrolytes in the body, contributing to headaches.
- Dose Adjustments: Some people experience headaches after the first dose or during the initial titration phase as their body adjusts to the medication.
How to Manage or Prevent Zepbound-Related Headaches
Zepbound-related headaches can often be prevented or treated. Some strategies include:
- Stay Well-Hydrated: Drink water regularly throughout the day, especially if appetite is reduced or there are gastrointestinal symptoms. Carrying a water bottle can help you remember.
- Maintain Regular Meals: Even with appetite suppression, eat balanced meals at consistent times to avoid low blood sugar. If calorie reduction is part of the weight loss plan, consult a provider about safe meal structures.
- Monitor for Other Side Effects: Pay attention to symptoms such as nausea or vomiting since they can increase dehydration and headache risk. Managing these symptoms with prescribed or over-the-counter remedies (if approved) can help prevent headaches.
- Consider Over-the-Counter Medications: For mild headaches, medications like acetaminophen may be used if a health provider approves, as these do not interact significantly with Zepbound.
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When to Contact a Doctor
Seek medical attention if headaches become persistent, severe, or are accompanied by other worrisome symptoms, such as vision changes, chest pain, or fever. Persistent vomiting, confusion, or signs of severe dehydration (dry mouth, rapid heartbeat, minimal urination) are also reasons to consult a healthcare professional, as these could indicate a more serious reaction.
Conclusion
Headaches linked to Zepbound may be temporary and can typically be managed with good hydration and symptom monitoring. Communicate openly with your healthcare provider to best manage side effects so you can continue your treatment while staying safe.
References
- Colorado, M., Gomez Miranda, J., & Arias-Morales, C. E. (2025). Unanticipated Adverse Events With Tirzepatide: Three Cases Underscoring the Importance of Postmarketing Monitoring. JCEM case reports, 3(10), luaf195. https://doi.org/10.1210/jcemcr/luaf195
- Mishra, R., Raj, R., Elshimy, G., Zapata, I., Kannan, L., Majety, P., Edem, D., & Correa, R. (2023). Adverse Events Related to Tirzepatide. Journal of the Endocrine Society, 7(4), bvad016. https://doi.org/10.1210/jendso/bvad016
- Zepbound [package insert]. Updated July 2025. Eli Lilly and Company. Accessed on September 7, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b
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Drug information
- Zepbound Information for Consumers
- Zepbound prescribing info & package insert (for Health Professionals)
- Side Effects of Zepbound (detailed)
- Zepbound user reviews (456)