Does Zepbound cause headaches?

In this article:

• Zepbound and headaches
• Causes
• Prevention
• Tips for taking Zepbound

In this article

• Zepbound and headaches
• Causes
• Prevention
• Tips for taking Zepbound

Zepbound (tirzepatide) is a weekly injectable medication that is FDA approved for chronic weight management in overweight or obese adults, and to treat obstructive sleep apnea in adults with obesity. It contains the same active ingredient as Mounjaro, which is used to lower blood sugar levels in people with Type 2 diabetes. Because it mimics the effects of two different hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), it potentially has more benefits than drugs that only mimic GLP-1, like Ozempic.

It also has a similar side effect profile to Ozempic, causing nausea, vomiting, stomach pain, constipation, and—for a small number of people—an increase in headaches. This is an uncommon side effect, and Zepbound doesn’t directly cause headaches; however, some of its other side effects can trigger head pain. Here’s what to know.

Are headaches a common side effect of Zepbound?

Headaches are one of the possible side effects of Zepbound, but they’re not considered one of the drug’s most common side effects. Zepbound’s manufacturer, Eli Lilly, doesn’t include headache as a side effect because it didn’t occur in 2% or more of people taking the drug during clinical trials. 

Since then, some studies suggest a higher percentage of people on Zepbound experiencing headaches, but it’s hard to pinpoint the exact amount. For example, 9.4% of participants in a 2023 phase-3 trial reported headache, but so did 7.5% of participants in the placebo group.

Some people may be more likely to get a headache while taking Zepbound than others, including people on a higher dose. One study found that headaches occurred more often when people were taking a 10- or 15-milligram dose compared to a 5-milligram dose. Headaches have also been reported more often by women than men, says Rani Aravamudhan, MD, a physician based in the Detroit metropolitan area. However, that doesn’t necessarily mean women are more susceptible. “Currently, there is not enough data, evidence, or clinical studies [to say] who might be at higher risk for headaches with Zepbound or other GLP-1 meds,” Dr. Aravamudhan notes.

Potential side effects of Zepbound include:

• Nausea, indigestion, and vomiting
• Diarrhea or constipatio
• Abdominal pain
• Injection site reactions
• Fatigue
• Allergic reactions
• Belching
• Hair loss
• Heartburn
• Lightheadedness
• Shakiness

Rare, but serious side effects include:

• Severe stomach problems
• Kidney problems, including kidney failure
• Thyroid cancer or thyroid tumors
• Non-arteritic anterior ischemic optic neuropathy (NAION)

Pregnant or breastfeeding individuals and those with certain health conditions such as pancreatitis, gallbladder disease, diabetic retinopathy, and Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) should consult a healthcare provider for medical advice before starting Zepbound.

Why does Zepbound sometimes cause headaches?

If Zepbound isn’t known for causing headaches, you might be wondering why it seems like you always get a headache within a few days of taking your weekly dose. There are a few reasons why this might be happening, but Dr. Aravamudhan says the cause isn’t Zepbound directly—instead, it’s the effects Zepbound is having on your body.

Low blood sugar

Zepbound’s active ingredient, tirzepatide, effectively lowers your blood sugar. While this is good news for people with Type 2 diabetes who need help managing their glucose levels, it can result in blood sugar that’s too low for some people, also known as hypoglycemia. A common symptom of hypoglycemia is headache.

This may be more common in people using Zepbound to treat Type 2 diabetes, especially if you are also taking other medications that lower your blood sugar. For example, one clinical trial found that 4.2% of people with diabetes taking Zepbound experienced hypoglycemia compared to 1.3% of people in the placebo group.

Dehydration

Gastrointestinal side effects like nausea, vomiting, and diarrhea are common with Zepbound; in fact, nausea is the most common side effect, occurring in 25-28% of people. If severe or persistent enough, nausea and other GI symptoms can quickly lead to dehydration. Headaches are a typical sign of dehydration.  

Changes in eating habits

Two common side effects of Zepbound—upset stomach and loss of appetite—can cause you to change your dietary habits. Zepbound is designed, in part, to reduce your appetite in order to help with weight loss, but even though reduced appetite is to be expected, some people experience it more than others.

If you persistently feel sick to your stomach or totally uninterested in food, you might skip meals, go for hours without eating a small snack, or rely on carb- and sugar-heavy comfort foods like crackers, white rice, and soda. All of these things can lead to abrupt changes in your blood sugar levels, a known cause of headaches for people with diabetes.

Loss of electrolytes

Electrolytes are essential minerals, like sodium, magnesium, potassium, and calcium, that help balance fluid levels in your body (among many other important tasks!). Dr. Aravamudhan says people taking Zepbound and having severe GI distress, like frequent vomiting or diarrhea, are at risk of electrolyte loss or imbalance, and headaches are a common symptom. Between 19% and 23% of people on Zepbound report diarrhea, and 8% to 13% report vomiting.

Do other GLP-1s cause headaches?

Other GLP-1 medications can cause headaches for the same reasons Zepbound can: sudden drops in blood sugar, dehydration, and changes to your eating habits that lead to electrolyte loss and less food intake. Like Zepbound, the manufacturers of Ozempic don’t report headache as a side effect based on their clinical trials.

Your experience with Wegovy, on the other hand, could be different. Even though it contains the same active ingredient as Ozempic (semaglutide), it’s typically prescribed at a higher dose because of its approval as a weight loss treatment. In clinical trials, 14% of people taking the highest dose of Wegovy reported headache as a side effect compared to 10% of the placebo group.

How to avoid Zepbound headaches

According to Wiljon Beltre, MD, bariatric and metabolic surgeon and founder of Beltre Bariatrics in Florida, Zepbound headaches are often described as “nagging” headaches, meaning they’re usually not debilitating or severe and are short-lasting. But if you’re trying to avoid getting them on Zepbound, there are a few things you can do.

• Eat small, healthy meals: What you eat, and when you eat it, can help you avoid sudden drops in your blood sugar. Try eating smaller meals every 3-4 hours that have a good mix of complex carbohydrates, protein, fat, and fiber to keep your blood sugar levels stable. Avoid meals high in added sugar.
• Stay hydrated: Dehydration is common with GLP-1 drugs (especially if you have any vomiting or diarrhea) and often causes headaches. If you’re having trouble keeping down plain water, bone broth is a good substitute because it also has nutrients in it that you may be missing if you’re eating less. You can also opt for an electrolyte drink if you’ve had stomach problems and need hydration with benefits.
• Avoid alcohol: Although alcohol isn’t off-limits for people taking Zepbound, it can increase the risk of side effects like low blood sugar and nausea. Alcohol acts as a diuretic as well, increasing urine production and contributing to dehydration. Dr. Aravamudhan says avoiding alcohol with Zepbound can be helpful in reducing your risk of headache. 

If you get a headache anyway after making these changes, OTC pain relievers like acetaminophen, ibuprofen, and aspirin are generally safe to take with Zepbound. They might not work quite as well as you’re used to, however: “Taking oral medication while using Zepbound may make [it] less effective,” says Dr. Beltre, “[because] Zepbound can impact your body’s ability to absorb oral medication, resulting in a lower level of the drug in your system.”

It’s a good idea to consult with a healthcare professional before taking any other oral medications while on Zepbound, advises Dr. Beltre.

How to take Zepbound to reduce side effects

Many people taking Zepbound notice fewer side effects the longer they’re on the medication. Dr. Beltre says most side effects, including headaches, go away within a few days to a couple of weeks of starting Zepbound. 

In the meantime, there are a few ways you can reduce the side effects of GLP-1 medications, including Zepbound:

• Eat slowly and try to eat smaller meals more often
• Eat bland foods, like toast, rice, and bananas 
• Stop eating when you feel full
• Avoid foods that are overly greasy, spicy, sweet, or fatty 
• Stay hydrated, using water-rich foods like soup, broth, and gelatin, if drinking too much water worsens your symptoms
• Drink ginger tea or chew on ginger root
• Don’t overdo it with fiber; start slow and gradually increase 
• Don’t eat too close to bedtime or lie down right after a meal
• Get plenty of light exercise

If you’re still experiencing side effects with Zepbound after several weeks, despite making some lifestyle changes, Dr. Beltre says you should talk to your healthcare provider. They may prescribe you another medication to help relieve your symptoms (like an antiemetic if you’re vomiting a lot), or they may want to lower your dose or switch you to another GLP-1 with a lower risk of headache.