GLP-1 Side Effects: Common, Serious, and When to Call a Doctor

The most common GLP-1 side effects are nausea, diarrhea, vomiting and constipation, and in the large trials they were usually mild to moderate and eased over time. The serious ones are less common but need prompt attention: pancreatitis, gallbladder disease, dehydration leading to kidney injury, and low blood sugar in people also taking insulin. The boxed warning about thyroid tumors is based on rodent studies, and whether it applies to humans is unknown.

Everything below comes from the FDA-approved prescribing information for Wegovy (semaglutide) and Zepbound (tirzepatide) and from the trials behind them. It applies to the approved products. Compounded or online versions have not been studied in the same way.

Common GLP-1 side effects: how often they happen

Stomach and bowel effects dominate. The table shows rates from the adult weight-reduction trials in each drug’s label, comparing the drug (at the highest dose studied for weight loss) with placebo.

Sources: Wegovy prescribing information and Zepbound prescribing information on DailyMed. The two sets of trials enrolled different people, so the columns should not be read as a head-to-head comparison.

Other reactions listed as common (at least 5%) on one or both labels include abdominal pain, headache, fatigue, indigestion, dizziness, bloating, belching, wind, reflux, injection site reactions and hair loss. The Wegovy label also lists dysesthesia, an abnormal or unpleasant skin sensation.

Why the stomach is affected

Part of how these drugs work is by slowing the rate at which food leaves the stomach; the Zepbound label refers to this delayed gastric emptying directly when it explains the contraceptive interaction below. Food sitting in the stomach for longer is a plausible contributor to the nausea, early fullness, belching and reflux listed among the common reactions.

The same effect is behind two of the less obvious warnings: the risk of stomach contents being inhaled during anaesthesia, and the reduced reliability of oral contraceptives noted on the Zepbound label. Neither is common, but both are easy to prevent when the people treating you know you take a GLP-1 drug.

Do they settle down?

Usually. In the STEP 1 trial, which followed 1,961 adults for 68 weeks, nausea and diarrhea were the most common adverse events and were “typically transient and mild-to-moderate in severity and subsided with time.” Still, 4.5% of people on semaglutide stopped because of gastrointestinal events, against 0.8% on placebo. On the Zepbound label, between 1.9% and 4.3% stopped for gastrointestinal reasons depending on dose, against 0.5% on placebo.

Both drugs are started low and increased in steps, partly to limit these effects. That dose schedule is set by the prescriber and the label, which is one reason vials with uncertain contents or measuring confusion cause trouble; see compounded GLP-1 dosing errors.

Serious side effects listed on the label

These are the Warnings and Precautions on the Wegovy and Zepbound labels. Most are uncommon, but each has symptoms worth knowing.

Acute pancreatitis

In the Wegovy weight-reduction trials, acute pancreatitis was confirmed in four people on the drug (0.2 cases per 100 patient-years) and one on placebo. In the pooled Zepbound weight-reduction trials, the rate was 0.2% in both the drug and placebo groups. The Wegovy label describes the warning sign as persistent or severe abdominal pain, sometimes radiating to the back, with or without nausea or vomiting.

Gallbladder disease

Both labels carry a warning for acute gallbladder disease. Gallstones (cholelithiasis) were reported in 1.6% of adults on Wegovy injection versus 0.7% on placebo. With Zepbound, cholelithiasis was 1.1% versus 1%, and cholecystitis (gallbladder inflammation) 0.7% versus 0.2%. The Wegovy Medication Guide lists the symptoms as upper stomach pain, fever, yellowing of the skin or eyes, and clay-colored stools.

Dehydration and kidney injury

Vomiting and diarrhea can cause enough fluid loss to injure the kidneys. The Medication Guide tells patients to contact their provider right away about nausea, vomiting or diarrhea that does not go away.

Low blood sugar

The Wegovy label lists hypoglycemia among common reactions in people with type 2 diabetes, and says the risk increased when semaglutide was used with insulin. It tells prescribers to consider lowering the dose of insulin or other insulin secretagogues when starting. Symptoms listed in the Medication Guide include dizziness, sweating, shakiness, blurred vision, confusion and a fast heartbeat.

Other label warnings

• Severe gastrointestinal reactions. Wegovy is not recommended for people with severe gastroparesis. Post-marketing reports listed on the label include ileus and intestinal obstruction.
• Allergic reactions, including swelling of the face, lips, tongue or throat.
• Diabetic retinopathy complications in people with type 2 diabetes.
• Heart rate increase.
• Aspiration under anaesthesia. Because these drugs slow stomach emptying, both labels warn about pulmonary aspiration during general anaesthesia or deep sedation. The label tells patients to inform providers before any planned surgery or procedure.
• Oral contraceptives. The Zepbound label says it may reduce the effectiveness of oral hormonal contraceptives, and advises a non-oral or added barrier method for four weeks after starting and after each dose increase.

The thyroid tumor boxed warning

Both labels carry a boxed warning for thyroid C-cell tumors. The basis is rodent studies, in which the drugs caused these tumors. The labels state it is unknown whether they cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans.

Because of that uncertainty, the drugs are contraindicated in anyone with a personal or family history of MTC or with multiple endocrine neoplasia syndrome type 2 (MEN 2). The label lists a lump in the neck, trouble swallowing, shortness of breath and persistent hoarseness as symptoms to report.

What happened to the suicidal thoughts warning

The weight-loss labels used to carry a warning about suicidal behavior and ideation. On January 13, 2026 the FDA asked manufacturers to remove it from Saxenda, Wegovy and Zepbound. Its review included a meta-analysis of 91 placebo-controlled trials with 107,910 patients, which found no increased risk, and an FDA Sentinel study of more than 2.2 million new users with type 2 diabetes, which found no increased risk of intentional self-harm. The FDA still asks patients to tell their health care professional about new or worsening depression or suicidal thoughts.

Side effects and when to seek care

Side effects with compounded and unapproved products

The label rates above apply to approved, correctly dosed products. As of May 31, 2026 the FDA had received 990 adverse event reports linked to compounded semaglutide and more than 730 to compounded tirzepatide, according to its page on unapproved GLP-1 drugs, which notes that underreporting is likely. Dosing errors from multi-dose vials have caused the same stomach effects at much greater intensity. See compounded semaglutide vs brand, counterfeit Ozempic signs and, for the unapproved triple agonist sold online, retatrutide risks.

You can report a side effect from any GLP-1 product, approved or not, through FDA MedWatch. If you have a planned operation, the single most useful step from the list above is to tell the anaesthetist you take a GLP-1 drug, because the label’s aspiration warning depends on them knowing.

Sources

• DailyMed: Wegovy (semaglutide) prescribing information
• DailyMed: Wegovy Medication Guide
• DailyMed: Zepbound (tirzepatide) prescribing information
• Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med, 2021
• FDA: FDA Requests Removal of Suicidal Behavior and Ideation Warning from GLP-1 RA Medications (January 13, 2026)
• FDA: FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight Loss
• FDA: MedWatch Safety Information and Adverse Event Reporting Program