Can Zepbound cause headaches?

If you’ve been taking Zepbound (tirzepatide) or thinking about trying the weight loss injection, you may already be familiar with some of its more well-known side effects (e.g. nausea, diarrhea, vomiting). But you may still be wondering whether Zepbound can cause headaches.  

While headache is not listed as a side effect on the prescribing information for Zepbound, anecdotal reports of headaches experienced on the drug are starting to pop up across social media, such as on Reddit and TikTok. 

So, can Zepbound cause headaches or not? Ahead, we—with help from medical experts—answer that question, break down why Zepbound can cause headaches for some, and offer tips to prevent and treat the potential side effect.

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Headaches can be a common symptom of several medications that are similar to Zepbound, such as Wegovy (semaglutide) and Saxenda (liraglutide). However, in clinical trials for Zepbound, headaches were not reported as a side effect. The most common side effects of Zepbound—meaning at least 5% of people reported them in clinical trials—include: nausea, diarrhea, vomiting, constipation, abdominal pain, upset stomach or indigestion, injection site reactions, among others. 

Take a quick visit to the r/Zepbound subreddit, though, and it feels like you can throw the proverbial stone and land on a thread discussing whether Zepbound can cause headaches. In a post titled, “Headaches?”, for example one Reddit user asks, “Has anyone else noticed more frequent headaches since starting Zepbound?” Much of the community responded in the affirmative, even describing their ailments: “a slight frontal headache [on] day one or two after my shot,” “a very bad headache on day 2 after the shot. I wake up feeling hungover.” And the same is true of another Reddit thread on the topic. It isn’t all negative, though; for example, some users’ said their headaches ultimately “went away” while others shared they experienced relief by “drink[ing] more water.”  

So, what’s the deal? Can Zepbound cause headaches and if so, why? 

As mentioned above, headache is not included as a side effect on the prescribing information for Zepbound. But large-scale reviews of tirzepatide (the active ingredient in Zepbound) have documented reports of headaches. In one analysis of ten clinical trials,for example, between 4-11% of people reported headaches when taking Mounjaro, a diabetes medication that contains the same active ingredient as Zepbound. People taking the higher dosage strengths of tirzepatide were more likely to report headache. 

In another study of people with type 2 diabetes, nearly 14% of those taking Mounjaro reported headache as a side effect. However, about 8% of those taking a placebo also reported headache. And in a recent 2023 study of Zepbound, 9.4% of participants reported headache—but so did 7.5% of people who were taking a placebo. Essentially, it’s unclear if the medication or other factors are to blame since participants experienced headaches both while taking Zepbound and the placebo.

Diagnosing the cause of headaches while on Zepbound can be a bit tricky. Common causes can include dehydration and hypoglycemia (low blood sugar), both of which may occur when taking Zepbound. 

“The underlying causes of these headaches are often complex and can include dehydration and electrolyte imbalances,” shares Praveen Guntipalli, MD, a board-certified physician specializing in internal medicine and obesity medicine and Medical Director and Owner of Sanjiva Medical Spa in Dallas, Texas. “Zepbound makes you feel full more quickly. This can inadvertently lead to reduced fluid intake as patients eat less.” 

Zepbound can also cause nausea and vomiting, which can lead to dehydration, too, says James Hook, MD, wellness professional at Neurogan Health. 

Dehydration not only can cause headaches on Zepbound (and in general) but it can also increase the risk of more frequent or painful headaches for people with a history of migraines.   Moreover, studies show that among people with migraine disorder, those who drink more water on a daily basis tend to experience fewer, less severe headaches.   

“Additionally, some patients experience headaches induced by nausea or as a result of hypoglycemia, especially when their eating patterns change due to the medication's appetite suppression effects,” Dr. Guntipalli says. 

In particular, people taking Zepbound who have type 2 diabetes may be more likely to experience low blood sugar, especially if they’re also taking insulin or insulin secretagogues (e.g. sulfonylurea). Your healthcare provider should advise you of what to do if you experience hypoglycemia. Common approaches include keeping a quick source of sugar on hand, such as glucose tablets, juice, or a glucagon shot. It’s also a good idea to learn to recognize the signs of low blood sugar, which, in addition to headache, may include: dizziness, sweating, irregular heartbeat or palpitations, shakiness, hunger, confusion or drowsiness, blurry vision, and slurred speech. 

Headaches can be a frustrating part of everyday life, even if you aren’t taking Zepbound. On any given day, roughly 16% of the global population experiences a headache, whether from stress, lack of sleep, alcohol, or another reason (e.g. even another medication).  

“Patients can reduce or treat headaches by ensuring that they stay hydrated, follow a nutritious diet, and [manage] their stress levels through relaxation techniques like yoga or light exercises,” Dr. Hook says.

“It’s crucial for patients to understand the multifaceted nature of these headaches and the importance of maintaining adequate hydration,” Dr. Guntipalli explains. “I consistently advise my patients to enhance their hydration habits. Simple strategies like setting regular reminders to drink water, using a gallon water bottle to monitor intake, or always carrying a water bottle can be very effective in preventing dehydration-related headaches.”

Other options for treating and reducing headaches include resting in a dark, quiet place, and placing a cool, damp cloth over your head. You can also take over-the-counter pain relievers, such as acetaminophen, aspirin, or ibuprofen. While Zepbound is not known to have any dangerous interactions with pain relievers, some of these may have interactions with other medications, so check with your healthcare provider to be sure you take the right one for you before popping any pills.

It may help to keep a headache diary so you can identify what’s triggering your headaches on a Zepbound. This can be as simple as just jotting a few notes down in a notebook or the notes app on your phone. Keep track of the following:

• The day and time you experienced your headache

• What you were doing and where you were when the headache started

• How long your headache lasted

• Anything you did to relieve your headache, and if it worked

• How much you slept the night before

• What you ate and drank within the last 24 hours

In many cases, headaches are annoying but manageable. But if yours are persistent, sudden, and/or so severe they impact your quality of life, it’s time to check in with your healthcare provider, Dr. Hook says. “They will be able to recommend the best course of action.” 

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Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

Current version

May 08, 2024

Written by

Amelia Willson

Fact checked by

Patricia Weiser, PharmD

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About the medical reviewer

Patricia Weiser, PharmD

Patricia Weiser, PharmD is a licensed pharmacist and medical writer. She has more than 14 years of clinical experience in community and hospital pharmacy.