Semaglutide (Wegovy) and tirzepatide (Zepbound) are prescription medicines for weight management, used with a reduced-calorie diet and more physical activity. Both come as a once-weekly shot, and Wegovy also comes as a daily tablet [1, 2]. Like any medicine, they can cause side effects. The most common ones affect the stomach and bowels and happen most often while the dose is going up [1, 2].
Common side effects
In the trials behind each medicine’s FDA label, people got the medicine or a placebo (an inactive look-alike shot), plus diet and activity advice. Wegovy figures are from three trials of the 2.4 mg weekly dose lasting up to 68 weeks (2,116 people on Wegovy, 1,261 on placebo). Zepbound figures are from two 72-week trials, shown for each weekly dose [1, 2].
| Side effect | Wegovy 2.4 mg vs placebo | Zepbound 5 / 10 / 15 mg vs placebo |
|---|---|---|
| Nausea | 44% vs 16% | 25% / 29% / 28% vs 8% |
| Diarrhea | 30% vs 16% | 19% / 21% / 23% vs 8% |
| Vomiting | 24% vs 6% | 8% / 11% / 13% vs 2% |
| Constipation | 24% vs 11% | 17% / 14% / 11% vs 5% |
| Stomach (abdominal) pain | 20% vs 10% | 9% / 9% / 10% vs 5% |
| Indigestion | 9% vs 3% | 9% / 9% / 10% vs 4% |
| Tiredness | 11% vs 5% | 5% / 6% / 7% vs 3% |
| Dizziness | 8% vs 4% | 4% / 5% / 4% vs 2% |
| Belching | 7% vs less than 1% | 4% / 5% / 5% vs 1% |
| Heartburn (reflux) | 5% vs 3% | 4% / 4% / 5% vs 2% |
| Hair loss | 3% vs 1% | 5% / 4% / 5% vs 1% |
| Injection-site reactions | 1.4% vs 1% | 6% / 8% / 8% vs 2% |
Overall, 73% of people on Wegovy and 47% on placebo reported a stomach or bowel side effect. With Zepbound, it was 56% at each dose, compared with 30% on placebo [1, 2]. Wegovy’s label also lists headache (14% vs 10%). Zepbound’s lists allergic reactions, mostly rash or itching (5% at each dose vs 3%) [1, 2]. Both labels note that rates from different medicines’ trials can’t be compared directly and may differ from everyday practice [1, 2].
Hair loss was linked to weight loss in the trials and was more common in women. On Wegovy 2.4 mg, 4% of women and 0.9% of men reported it. On Zepbound, it was 7.1% of women and 0.5% of men [1, 2]. At Wegovy’s highest dose, 7.2 mg (Wegovy HD), 72-week trials found that 22% of people reported changes in skin feeling, such as tingling or burning, vs 6% on 2.4 mg [1].
Why side effects are most common early on
GLP-1 medicines slow down how fast food leaves your stomach [1, 2]. This slowing is greatest early on and lessens over time, and an expert panel notes that nausea is most common in the first 4 to 5 weeks of treatment [2, 3]. In the trials, stomach and bowel side effects were reported most often while the dose was being raised. With Zepbound, most nausea, vomiting and diarrhea happened during that time and eased later [1, 2].
That’s why both medicines start at a low dose and step up about every 4 weeks. The labels say this lowers the risk of stomach and bowel side effects [1, 2]. See starting a GLP-1 for the steps.
Side effects led some people to stop: 6.8% on Wegovy vs 3.2% on placebo, and 4.8% to 6.7% on Zepbound (depending on dose) vs 3.4% [1, 2]. Most who stopped Zepbound because of side effects did so in the first few months, due to stomach and bowel symptoms [2].
How side effects are managed
What your clinician may do
- Slow down the steps. If a dose is hard to tolerate while it’s being raised, Wegovy’s label says to consider waiting 4 more weeks before the next increase [1].
- Choose a lower long-term dose. Both medicines have more than one approved maintenance (long-term) dose, chosen based on how well it works and how well you tolerate it. Zepbound’s label says to consider a lower one if a higher dose isn’t tolerated [1, 2].
- Look for other causes and treat symptoms. An expert panel recommends checking for other causes of severe or lasting symptoms, treating the specific symptom and, if needed, pausing the medicine until symptoms settle [3].
Use your medicine exactly as prescribed, and don’t change your dose on your own [1, 2]. If you miss 2 or more weekly doses of Wegovy in a row, the label says to restart the dose steps at a lower dose. This lowers the risk of stomach and bowel side effects [1].
What you can do
The same expert panel suggests these habits when you start treatment [3]:
- Eat slowly, and eat smaller portions [3].
- Stop eating as soon as you feel full [3].
- Pick easy-to-digest, lower-fat foods, and limit spicy foods, dressings and store-bought sauces [3].
- Don’t lie down right after a meal, and avoid eating close to bedtime [3].
- Drink fluids in small sips through the day. The Medication Guides say drinking fluids helps lower your chance of dehydration [1, 2, 3]. If it’s hard to keep liquids down, try small sips of water or ice chips [4].
- For constipation, get enough fiber, drink plenty of water and stay active [3].
- Keep a food diary to spot foods or meal times that make symptoms worse [3].
For more ideas, see eating well on a GLP-1. Most side effects of weight management medicines are mild and often get better as you keep taking the medicine [5].
Serious risks listed in the labels
These are less common, but know the signs. Each one is a warning in both the Wegovy and Zepbound labels unless noted [1, 2].
- Thyroid tumors. Both labels have a boxed warning. Both medicines caused thyroid C-cell tumors in rodents; it isn’t known whether they do in people. Don’t use them if you or a family member has had medullary thyroid carcinoma (MTC), or if you have multiple endocrine neoplasia syndrome type 2 (MEN 2). Report a neck lump or swelling, hoarseness, trouble swallowing or shortness of breath [1, 2].
- Pancreatitis (an inflamed pancreas). Signs include severe stomach pain that won’t go away, sometimes spreading to your back, with or without vomiting. Stop the medicine and call your clinician right away [1, 2].
- Gallbladder problems. Gallstones and gallbladder inflammation were more common than with placebo. For example, gallstones were reported in 1.6% of adults on Wegovy shots vs 0.7% on placebo. Signs include upper stomach pain, fever, yellow skin or eyes, and clay-colored stools [1, 2].
- Dehydration and kidney injury. Vomiting and diarrhea can dehydrate you. Kidney injury, sometimes needing dialysis, has been reported, mostly in people who were dehydrated from stomach and bowel side effects [1, 2].
- Severe stomach and bowel problems. These were reported in 4.1% of people on Wegovy shots vs 0.9% on placebo, and in 1.7% to 3.1% on Zepbound vs 1%. Blocked bowels and severe constipation have been reported since approval. Neither medicine is recommended if you have severe gastroparesis (a stomach that empties very slowly) [1, 2].
- Low blood sugar. This is mainly a risk if you have diabetes, especially if you take insulin or a sulfonylurea (a type of diabetes medicine). In trials of people with type 2 diabetes, blood sugar below 54 mg/dL happened in 6.2% on Wegovy vs 2.5% on placebo. With Zepbound, it was 4.2% vs 1.3%, and 10.3% in people also taking a sulfonylurea. Your clinician may lower those diabetes medicines when you start. Signs include shakiness, sweating, dizziness, hunger and confusion, so ask your clinician how to spot and treat it [1, 2].
- Serious allergic reactions, including anaphylaxis and swelling under the skin (angioedema), have been reported [1, 2].
- Faster heart rate. This is a warning in Wegovy’s label. On average, Wegovy raised resting heart rate by 1 to 4 beats per minute vs placebo, and your clinician should check it during treatment [1]. Zepbound’s label reports an average rise of 1 to 3 beats per minute [2].
- Eye problems in type 2 diabetes. Rapid improvement in blood sugar can briefly worsen diabetic retinopathy (diabetes-related eye damage). In a 2-year trial of lower semaglutide doses in people with type 2 diabetes and high heart risk, eye complications happened in 3% vs 1.8% on placebo [1]. If you’ve had diabetic retinopathy, your eyes should be monitored [1, 2].
- Food in the lungs during anesthesia. Because these medicines slow stomach emptying, food or liquid has rarely gotten into the lungs during procedures with general anesthesia or deep sedation, even in people who fasted as told. Tell your surgical and anesthesia team you take a GLP-1 before any planned procedure. The labels say there isn’t enough data to know whether stopping the medicine beforehand helps, so let your care team guide you [1, 2].
Mood changes: no longer a label warning
Earlier Wegovy and Zepbound labels had a warning about suicidal thoughts and behavior, based on reports with older weight-loss medicines [6]. In January 2026, the FDA reported that its review of 91 placebo-controlled trials (107,910 people) and a study of more than 2 million people with type 2 diabetes found no increased risk with GLP-1 medicines. It asked drugmakers to remove the warning [6], and the current labels no longer include it [1, 2]. The FDA still advises telling your clinician about new or worsening depression, suicidal thoughts or unusual mood changes [6].
When to get medical care
Call 911 if you have:
- swelling of your face, lips, tongue or throat, trouble breathing or swallowing, or fainting, which can be signs of a serious allergic reaction [1, 2, 7]
- chest pain or pressure, especially with shortness of breath, a cold sweat, light-headedness, or pain in your arm, jaw, neck or back [8]
Get care the same day if you have:
- severe stomach pain that won’t go away, with or without vomiting (stop the medicine and call your clinician right away) [1, 2]
- signs of gallbladder problems, such as upper stomach pain, fever, yellow skin or eyes, or clay-colored stools [1, 2]
- nausea, vomiting or diarrhea that won’t go away, or signs of dehydration such as strong thirst, a dry mouth, peeing less, dark urine or dizziness [1, 2, 4]. Confusion, fainting, a racing heart or not peeing at all need medical help right away [4].
Call your clinician soon if you have:
- a racing or pounding heartbeat at rest that lasts several minutes [1]
- episodes of low blood sugar (treat them the way your clinician has shown you) [1, 2]
- vision changes, if you have type 2 diabetes [1, 2]
- a lump or swelling in your neck, hoarseness or trouble swallowing [1, 2]
- new or worsening depression or thoughts of suicide (in a crisis, call or text 988) [6]
- any side effect that bothers you or doesn’t go away [1, 2]
The bottom line
Stomach and bowel side effects, especially nausea, are common with Wegovy and Zepbound and most likely while your dose is going up. Gradual dose steps, smaller and lower-fat meals, stopping when you’re full and drinking enough fluids can help, and your clinician can adjust the plan. Serious problems such as pancreatitis, gallbladder disease, kidney injury from dehydration and allergic reactions are less common but need fast care. Ask your clinician which risks apply to you.
References
- Novo Nordisk. WEGOVY (semaglutide) injection, for subcutaneous use; WEGOVY (semaglutide) tablets, for oral use: prescribing information, Medication Guide and Instructions for Use. DailyMed, U.S. National Library of Medicine. Label revised June 2026 (effective June 18, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b
- Eli Lilly and Company. ZEPBOUND (tirzepatide) injection, for subcutaneous use: prescribing information, Medication Guide and Instructions for Use. DailyMed, U.S. National Library of Medicine. Label revised August 2026 (effective August 28, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b
- Gorgojo-Martínez JJ, et al. Clinical recommendations to manage gastrointestinal adverse events in patients treated with GLP-1 receptor agonists: a multidisciplinary expert consensus. Journal of Clinical Medicine. 2022. https://pmc.ncbi.nlm.nih.gov/articles/PMC9821052/
- MedlinePlus. Dehydration. U.S. National Library of Medicine. Last updated December 2023. https://medlineplus.gov/dehydration.html
- National Institute of Diabetes and Digestive and Kidney Diseases. Prescription medications to treat overweight and obesity. NIDDK, National Institutes of Health. Last reviewed June 2024. https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity
- U.S. Food and Drug Administration. FDA requests removal of suicidal behavior and ideation warning from glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications. FDA Drug Safety Communication. January 13, 2026. https://www.fda.gov/drugs/drug-safety-communications/fda-requests-removal-suicidal-behavior-and-ideation-warning-glucagon-peptide-1-receptor-agonist-glp
- MedlinePlus. Anaphylaxis. U.S. National Library of Medicine. Last updated December 2025. https://medlineplus.gov/anaphylaxis.html
- Centers for Disease Control and Prevention. About heart attack symptoms, risk, and recovery. CDC. 2026. https://www.cdc.gov/heart-disease/about/heart-attack.html
This article is for education only and isn’t a substitute for advice from your own clinician.