GLP-1 Side Effects Long Term: What Labels and Studies Say
In this guide
This article is for information only and is not medical advice. Talk to your prescriber or a qualified professional.
What do we know about GLP-1 side effects long term? Most side effects in the trials were stomach-related and showed up early, often during dose increases. The serious risks the FDA labels warn about apply for as long as you take the medicine: pancreatitis, gallbladder disease, kidney problems from dehydration, severe stomach problems and allergic reactions, plus a boxed warning about thyroid tumors seen in rodents. The longest trials we reviewed followed people for 2 years (STEP 5) and about 3 to 4 years (SELECT). Beyond that, the data are thinner. Your prescriber weighs these risks against the benefits for you.
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Key points
- Common side effects (nausea, diarrhea, vomiting, constipation) were mostly mild to moderate and most frequent early in treatment.
- The label warnings do not expire: they cover the whole time you take the medicine.
- In the 2-year STEP 5 trial, the authors called safety consistent with earlier trials. In SELECT, more people stopped semaglutide because of adverse events, but serious adverse events were lower than on placebo.
- Whether these medicines cause thyroid cancer in humans is unknown. People with certain thyroid cancer histories should not use them.
For how symptoms usually change over the first weeks and months, start with our GLP-1 side effects timeline.
Early side effects versus long-term risks
The first question is which side effects are common, and when. The labels list nausea, diarrhea, vomiting, constipation, abdominal pain, indigestion, burping, fatigue, headache and hair loss among the most common ones. In SURMOUNT-1, stomach side effects with tirzepatide happened mainly during dose escalation. In STEP 1, nausea and diarrhea with semaglutide were usually short-lived and mild to moderate, and eased over time.
The second question is what can happen at any point during treatment, even years in. That is what the label warnings describe.
What the labels warn about
These come from the Warnings and Precautions sections of the Wegovy and Zepbound prescribing information.
| Warning | What the label says, in plain words |
|---|---|
| Thyroid C-cell tumors (boxed warning) | Seen in rodents. Unknown whether this happens in humans. Not for people with a personal or family history of medullary thyroid carcinoma or with MEN 2. |
| Acute pancreatitis | Has been seen with GLP-1 medicines. Stop the medicine if pancreatitis is suspected. |
| Acute gallbladder disease | Gallstones and gallbladder inflammation were more common than on placebo. |
| Kidney injury from fluid loss | Vomiting and diarrhea can lead to dehydration and kidney problems. |
| Severe stomach problems | Sometimes severe. Not recommended for people with severe gastroparesis. |
| Serious allergic reactions | Anaphylaxis and angioedema have been reported. |
| Low blood sugar | Higher risk with insulin or a sulfonylurea. |
| Eye problems in type 2 diabetes | Diabetic retinopathy complications; people with a history of retinopathy should be monitored. |
| Food in the lungs during anesthesia | Tell your providers about any planned surgery or procedure with sedation. |
| Heart rate increase (Wegovy) | Mean resting increases of 1 to 4 beats per minute versus placebo in the weight trials. |
How often did gallbladder problems happen? In the Wegovy label’s adult weight trials, gallstones were reported in 1.6% on the injection versus 0.7% on placebo, and gallbladder inflammation in 0.6% versus 0.2%. In the Zepbound label’s pooled weight trials, gallstones were 1.1% versus 1%, and inflammation 0.7% versus 0.2%. The Wegovy label adds that substantial or rapid weight loss can raise gallstone risk.
After approval, reports also included bowel blockage (ileus and intestinal obstruction), severe constipation with fecal impaction, and acute kidney injury. The labels note that these voluntary reports cannot establish how often the problems happen or whether the medicine caused them. Our guides to GLP-1 constipation and stomach pain and cramps cover the everyday versions and the warning signs.
What the longest trials found
STEP 5: two years of semaglutide 2.4 mg
STEP 5 followed 304 adults with obesity, or overweight with a related condition, and no diabetes for 104 weeks.
| Event | Semaglutide | Placebo |
|---|---|---|
| Any stomach-related adverse event | 82.2% | 53.9% |
| Nausea | 53.3% | 21.7% |
| Serious adverse events | 7.9% | 11.8% |
| Stopped the medicine because of an adverse event | 5.9% | 4.6% |
| Gallbladder-related disorders | 2.6% | 1.3% |
| Acute pancreatitis | 0 | 0 |
The authors called the safety profile consistent with the other STEP trials. A trial this size cannot measure rare events well.
SELECT: about 3 years of exposure
SELECT enrolled 17,604 adults aged 45 or older with existing heart disease, a BMI of 27 or more and no diabetes. Mean time on semaglutide 2.4 mg or placebo was 34.2 months. Adverse events led to permanently stopping the medicine in 16.6% of the semaglutide group versus 8.2% on placebo. A later analysis reported fewer serious adverse events with semaglutide than with placebo in every BMI group, and weight loss sustained for up to 4 years.
Nutrition, muscle and bone
The 2025 joint nutrition advisory led by Mozaffarian lists other long-term concerns: not getting enough nutrients when eating much less, and loss of muscle and bone along with fat. It recommends attention to protein and resistance training. See GLP-1 muscle loss and protein on a GLP-1.
Mood
The current Wegovy and Zepbound labels show the earlier warning section on suicidal behavior and ideation as removed in February 2026. The 2025 advisory, written before that change, said risk and causation were not established and recommended screening and monitoring for worsening mood. Either way, tell your prescriber about any mood changes. More in GLP-1 anxiety and mood.
What is still unknown
- Thyroid tumors in humans. The labels say the human relevance of the rodent findings has not been determined.
- Use beyond about 4 years. The trials we reviewed ran up to about 4 years.
- Your own risk. Trial rates are averages in selected groups. Your prescriber reviews your history and other medicines.
When to call a clinician
When to call: severe stomach pain that will not go away, with or without vomiting, sometimes spreading to the back. Upper stomach pain, fever, yellow skin or eyes, or clay-colored stools. Nausea, vomiting or diarrhea that does not go away. A lump or swelling in the neck, trouble swallowing, shortness of breath or hoarseness that does not go away. Feeling your heart racing at rest for several minutes. Swelling of the face, lips, tongue or throat, or trouble breathing or swallowing: get medical help right away.
From the Wegovy Medication Guide and the Wegovy and Zepbound labels. The list is not complete. Related: feeling off after a dose and GLP-1 nausea.
A week of notes helps your prescriber see what is changing. This diary prints for your visit.
Frequently asked questions
What are the long-term side effects of GLP-1 drugs?
The labels warn about pancreatitis, gallbladder disease, kidney injury from dehydration, severe stomach problems, allergic reactions and thyroid tumors seen in rodents. These risks apply for as long as you take the medicine. The common stomach side effects were most frequent early in the trials.
Are GLP-1 medicines safe to take for years?
We cannot say whether a medicine is safe for you. In STEP 5 (2 years), the authors described safety as consistent with earlier trials. In SELECT (about 3 years of average exposure), more people stopped semaglutide because of adverse events than placebo, while serious adverse events were lower. Your prescriber weighs risks and benefits for you.
Do GLP-1 medicines cause thyroid cancer?
It is not known. The labels say semaglutide and tirzepatide caused thyroid C-cell tumors in rodents, and that the relevance to humans has not been determined. People with a personal or family history of medullary thyroid carcinoma or MEN 2 should not use them.
Do side effects go away over time?
For many people the common stomach side effects ease. In STEP 1 they were usually short-lived and subsided with time, and in SURMOUNT-1 they occurred mainly during dose escalation. Tell your prescriber about any side effect that persists.
Keep your own record
Dosinha’s free side-effect check-in records symptoms with severity, and the shot log shows which dose you were on when. That helps you notice patterns and share them with your prescriber. The app does not prevent or treat side effects. Try the free tools.
Sources
- DailyMed. Wegovy prescribing information and Medication Guide and Zepbound prescribing information. Labels posted 2026.
- Garvey WT, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine, 2022.
- Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). New England Journal of Medicine, 2023. Ryan DH, et al. Long-term weight loss effects of semaglutide in the SELECT trial. Nature Medicine, 2024.
- Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). NEJM, 2021. Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). NEJM, 2022.
- Mozaffarian D, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint advisory. Obesity, 2025.
This article is for information only and is not medical advice. Talk to your prescriber or a qualified professional.