GLP-1 side effects: what to expect and when to get help

In short: In trials of the FDA-approved medicines, the most common side effects of semaglutide and tirzepatide were digestive: nausea, diarrhea, vomiting and constipation, according to the Wegovy and Zepbound prescribing information. Most were mild to moderate, showed up early and after dose changes, and eased over time. Message your care team about anything that doesn't settle; call 911 for emergencies.

What are the most common side effects of semaglutide and tirzepatide?

Stomach and bowel symptoms top the list for both medicines. The Wegovy (semaglutide) and Zepbound (tirzepatide) labels name nausea, diarrhea, vomiting, constipation, belly pain, indigestion, burping, reflux and tiredness among the most common¹². In trials of these FDA-approved medicines, most of these effects were mild to moderate and temporary³⁴⁵.

Other side effects listed on the labels:

• Injection-site reactions such as redness, itching or a small firm area where you injected¹².
• Fatigue, which both labels list. No study has looked at it on its own¹².
• Hair shedding, which in trials was linked to weight reduction and was more common in women¹².
• Headache and dizziness, listed on the Wegovy label¹.

These findings come from studies of the FDA-approved products. Compounded semaglutide and compounded tirzepatide have not been studied in those trials. Compounded medications are not FDA-approved, and FDA does not review them for safety, effectiveness or quality⁶.

When do side effects start, and do they go away?

Side effects tend to show up in the first weeks and again after your care team raises your dose. The Zepbound label says most nausea, vomiting and diarrhea happened while the dose was being increased and decreased over time². Pooled trial data for FDA-approved semaglutide show the same pattern⁵. How long it lasts varies from person to person.

A few things to know:

• Symptoms can come back for a while after each dose change, then settle again²⁵.
• In those trials, few people stopped treatment because of stomach side effects³⁵.
• Don't change your dose, skip doses or space them out on your own to manage side effects. Tell your care team what's happening. Its licensed providers will decide whether and when to adjust.

What helps with nausea and other stomach side effects?

Small habit changes help most people. Expert guidance on GLP-1 medicines recommends eating slowly, eating smaller portions, stopping as soon as you feel full, and going easy on large, greasy or high-fat meals⁷⁸. Drink fluids through the day, especially if you're vomiting or have diarrhea. Message your care team if symptoms don't improve.

What the guidance suggests, by symptom:

• Nausea: smaller, more frequent meals. Eat only when hungry and stop when full. Don't lie down right after eating, and avoid eating close to bedtime⁷⁸. Sip drinks between meals rather than with them⁷. In the first days, some guidance suggests going easy on fatty or very high-fiber foods⁸.
• Vomiting or diarrhea: keep up your fluids. Avoid large or high-fat meals⁷⁸.
• Constipation: get enough fiber, drink plenty of water and stay active⁷.
• Reflux and burping: avoid alcohol and fizzy drinks, and don't lie down after meals⁷.
• Alcohol: keep it to a minimum. It can make stomach symptoms and dehydration worse⁸.

Ask your care team before taking any over-the-counter remedy, so they can check it against your other medicines.

How can I eat well and protect muscle with a smaller appetite?

Eat regular meals with enough protein, even when you're not hungry, and add strength training. A joint advisory from four US nutrition and obesity medicine societies recommends this pairing because some of the weight reduction on these medicines is lean mass, not fat⁸⁹. It's advice to support your health, not a guarantee about results.

The advisory recommends:

• Structured strength training at least three times a week, alongside regular aerobic activity⁸.
• Enough protein at each meal. A dietitian can help you set a target that suits you⁸.
• Not skipping meals. Going without food can make nausea worse⁸.

Which symptoms are warning signs?

Most side effects are uncomfortable but not dangerous. A few are serious. Severe belly pain that won't go away, signs of gallbladder trouble, dehydration, a serious allergic reaction, and low blood sugar if you take other diabetes medicines all need prompt care. The FDA-approved labels list these as warnings for both medicines¹².

• Pancreatitis: severe belly pain that won't go away, sometimes spreading to your back, with or without vomiting. The labels say to stop the medicine and get medical care right away¹².
• Gallbladder problems: pain in the upper belly, fever, yellow skin or eyes, or clay-colored stools¹².
• Dehydration and kidney problems: vomiting or diarrhea that won't stop, very little or dark yellow urine, strong thirst or dizziness. Dehydration can lead to kidney injury¹²¹⁰.
• Serious allergic reaction: swelling of your face, lips, tongue or throat, trouble breathing or swallowing, a severe rash, or feeling faint¹².
• Low blood sugar: shakiness, sweating, confusion, a fast heartbeat or hunger. The risk is higher if you also take insulin or a sulfonylurea¹².
• Vision changes if you have diabetic eye disease (retinopathy)¹².
• A lump or swelling in your neck, trouble swallowing, or hoarseness that won't go away. Both labels carry a boxed warning about thyroid C-cell tumors seen in rodents. It isn't known whether this happens in people¹².

Also tell any surgeon or anesthetist that you take one of these medicines before a procedure¹².

Can a measuring mistake cause side effects?

Yes. FDA has received reports of people drawing up many times their intended dose of compounded semaglutide from multi-dose vials. FDA's alert says "confusion between different units of measurement (e.g., milliliters, milligrams and 'units') may have contributed to dosing errors"¹¹. Some needed hospital care for vomiting, belly pain, dehydration, pancreatitis or gallstones¹¹. Measure exactly as your prescription label says, with the syringe supplied.

• On an insulin-style syringe, "units" measure volume, not medicine. How much medicine a unit holds depends on your vial¹¹.
• If your label, syringe or instructions don't match, stop and ask your care team or pharmacy before you inject¹¹.
• Our step-by-step guide covers measuring, sites and storage: How to give yourself an injection at home.
• If you think you took too much, call Poison Control at 1-800-222-1222. Call 911 if symptoms are severe.

Compounded medications are not FDA-approved, and FDA does not review them for safety, effectiveness or quality⁶.

Do these medicines affect mood?

On 13 January 2026, FDA asked for the suicidal thoughts and behavior warning to be removed from the Wegovy, Zepbound and Saxenda labels. FDA's drug safety communication says that "after a comprehensive review, FDA found no increased risk" of suicidal thoughts or behavior with these medicines¹². FDA still advises telling a healthcare provider about new or worsening depression, suicidal thoughts or unusual changes in mood¹².

If you have thoughts of harming yourself, call or text 988 (Suicide and Crisis Lifeline), or call 911¹².

What people often get wrong

• "Feeling sick means it's working." In pooled trial data for FDA-approved semaglutide, how people responded to treatment was largely unrelated to whether they had stomach side effects⁵. Feeling unwell is not a sign of progress, so don't push through severe symptoms.
• "Skipping meals helps the nausea." Expert guidance says the opposite: smaller, slower meals and stopping when full. Going without food can make nausea worse⁸.
• "Stomach pain is just part of it." Mild discomfort is common. Severe belly pain that won't go away, upper belly pain with fever or yellowing, or vomiting with signs of dehydration need care right away¹².
• "There's a suicide warning, so I shouldn't mention my mood." FDA removed that warning in January 2026, and also says to tell a healthcare provider about mood changes¹². Your care team wants to know.
• "A unit is a unit." On a syringe, units measure volume. The medicine in each unit depends on the vial, which is why FDA has seen serious measuring errors¹¹.