GLP-1 Side Effects: What the Trials and FDA Labels Actually Report

Semaglutide and tirzepatide can cause gastrointestinal side effects, and their approved product labels also describe less common but serious risks. The trial results below help frame a discussion with your clinician; they do not predict your individual experience or establish the quality of a telehealth service. The Wegovy and Zepbound label references were checked again in October 2026.

Gastrointestinal effects caused some trial participants to stop

Nausea, diarrhea, vomiting and constipation are reported with these medicines. In STEP-1, gastrointestinal events caused 4.5% of the semaglutide group to discontinue treatment, versus 0.8% on placebo¹. In SURMOUNT-1, discontinuation because of adverse events was 4.3%, 7.1% and 6.2% at the 5 mg, 10 mg and 15 mg tirzepatide doses, versus 2.6% on placebo. The most common adverse events were gastrointestinal and occurred primarily during dose escalation; those discontinuation figures concern all adverse events, not gastrointestinal events alone².

These were separate trials with different designs and populations, so the percentages are not a head-to-head comparison of tolerability. Ask your prescriber how to report persistent symptoms and how treatment decisions will be reviewed. Do not accelerate or change a prescribed schedule on the strength of a comparison page.

The boxed warning, in the FDA's own words

The Wegovy and Zepbound labels carry boxed warnings concerning thyroid C-cell tumors observed in rodents; whether these medicines cause such tumors in humans is unknown. Both are contraindicated for a personal or family history of medullary thyroid carcinoma or MEN 2. These are specific label precautions for the named products, not a claim that every GLP-1 product has identical labeling.^{3, 4}

Tell the prescriber about that history before treatment. A screening questionnaire or a laboratory result does not override a contraindication.

Pancreatitis and gallbladder disease are on the label — and gallbladder risk is now quantified

Both the Wegovy and Zepbound labels warn about acute pancreatitis^{3, 4}. Gallbladder disease is more than a label mention: a 2022 meta-analysis of 76 randomized trials covering more than 103,000 patients found GLP-1 receptor agonist use raised the risk of gallbladder or biliary disease overall (relative risk 1.37), with the risk concentrated in trials conducted for weight loss — a relative risk of 2.29 in that subgroup, versus 1.27 in diabetes and other-disease trials⁵. The pooled relative risks do not provide a personal risk estimate or establish that changing your dose schedule would prevent gallbladder disease. Discuss new or persistent abdominal symptoms with your clinician.

Diabetes and eye history need a separate conversation

In SUSTAIN-6, the long-term semaglutide cardiovascular trial in people with type 2 diabetes, retinopathy complications — vitreous hemorrhage, blindness, or conditions requiring treatment — occurred significantly more often on semaglutide than placebo (hazard ratio 1.76)⁶. Both the Wegovy and Zepbound labels now instruct monitoring patients with a history of diabetic retinopathy for progression^{3, 4}. The trial involved people with type 2 diabetes at high cardiovascular risk, using semaglutide doses different from the 2.4 mg weight-management regimen. It does not establish the same risk for every patient. Discuss your diabetes and eye history with the treating clinician.

What this means before surgery or a procedure

Because GLP-1s slow gastric emptying by design, a 2024 clinical-pharmacology review in Anaesthesia walked through the peri-operative implications: delayed emptying can leave more stomach contents than expected at the time of anesthesia, raising aspiration risk during sedation⁷. If you take a GLP-1 and have surgery, a dental procedure, or any sedation scheduled, tell the team beforehand — the anesthesia and prescribing teams should decide the plan together. Current Wegovy and Zepbound labels also describe rare postmarketing aspiration reports and say evidence is insufficient to establish whether temporarily stopping treatment reduces the risk. Do not use this article to decide when to stop or restart a medicine.^{3, 4} Our surgery and endoscopy guide compares the dated guidance and procedure studies, with questions to bring to the treating team.

Compounded vials add a risk the pivotal trials never tested: the dose itself

A 2023 poison-control case series described three adverse events after incorrectly administering semaglutide from compounding pharmacies or an aesthetic spa. Two patients reported tenfold dosing errors. One reported receiving a vial and syringes without pharmacist counseling, and one reported measurements in milliliters and units rather than milligrams.⁸

Three cases cannot tell us how frequently these errors occur or establish a single cause for every compounded-medication problem. They do show why the exact concentration, prescription, syringe markings and instructions need to agree. Use our vial-label guide to prepare questions for the dispensing pharmacist. Our compounded-medication guide explains the separate questions about the product and its source.

Ask about the monitoring plan, not just the test count

Ask who reviews your history, how you reach a clinician between refills and what happens when symptoms or results need follow-up. Our lab-testing and monitoring guide separates label instructions from an advertised test package; the provider checklist puts those questions alongside price and access.

Clinical oversight and labs-and-monitoring account for 35% of our WeighScore formula. Those recorded editorial marks do not measure clinical outcomes or prove that a provider carries out every label precaution. Confirm the arrangements for your own care rather than treating a high score as medical clearance.

Questions about contraception need the exact medicine and route too. Our GLP-1 and birth-control guide compares the current US label instructions and the questions to discuss before starting treatment or changing a dose.

Put the evidence beside your own health history

Treatment benefits and adverse effects need to be weighed together with a clinician who knows your history. Our benefits beyond weight loss guide provides additional study context. Use the provider reviews to investigate costs and terms, and bring medical questions to your treating team.