In SURMOUNT-1, the 72-week trial of tirzepatide in 2539 adults with obesity and no diabetes, adverse events caused treatment discontinuation in 4.3% of the 5 mg group, 7.1% of the 10 mg group, 6.2% of the 15 mg group and 2.6% of the placebo group (PMID 35658024). Gastrointestinal events were the most common, most were mild to moderate, and they occurred primarily during dose escalation.
Those four numbers are more informative than a list of symptoms, because they say how many people found the drug intolerable enough to stop. Roughly 93 to 96 in every 100 did not. This page works outward from that: who stopped, at which dose, how severe the events were, and which of the label's warnings sit outside the trial averages entirely.
- Discontinuation for adverse events in SURMOUNT-1 ran 4.3% to 7.1% across the three tirzepatide doses against 2.6% on placebo, and did not climb cleanly with dose.
- Pooled across SURMOUNT-1 to -4, between 27.8% and 72.8% of tirzepatide participants reported at least one gastrointestinal event, against 12.2% to 32.5% on placebo.
- Severe or serious gastrointestinal events were reported in 0.3% to 5.6% of tirzepatide participants across those four trials.
- The events cluster during dose escalation, and a mediation analysis found nausea, vomiting, diarrhoea and dyspepsia accounted for at most 3.1% of the weight reduction.
Who stopped, and at which dose
The cleanest severity signal in any trial is the discontinuation rate, because it is a decision rather than a tick box. SURMOUNT-1 ran three doses against placebo for 72 weeks in the same population, so the four figures are directly comparable.
| Group | Discontinued because of an adverse event | Mean weight change at 72 weeks |
|---|---|---|
| Tirzepatide 5 mg | 4.3% | -15.0% |
| Tirzepatide 10 mg | 7.1% | -19.5% |
| Tirzepatide 15 mg | 6.2% | -20.9% |
| Placebo | 2.6% | -3.1% |
Note what the middle column does not do. It does not rise with dose. The 10 mg group had the highest discontinuation rate in the trial, above the 15 mg group, which is not what a simple dose-toxicity story predicts and is a reminder that these are single-trial figures with confidence intervals around them rather than fixed properties of each dose. The dose ladder itself is set out in our tirzepatide dosage chart.
The pooled picture across four trials
A 2025 post-hoc analysis pooled gastrointestinal adverse events across SURMOUNT-1 through SURMOUNT-4, which between them cover adults with and without type 2 diabetes, 72 to 88 weeks, and both fixed and maximum tolerated dosing (PMID 39789843). As ranges across those arms:
| Measure | Tirzepatide arms | Placebo arms |
|---|---|---|
| Reported at least one gastrointestinal event | 27.8% to 72.8% | 12.2% to 32.5% |
| Severe or serious gastrointestinal event | 0.3% to 5.6% | Not reported as a range |
| Stopped treatment because of a gastrointestinal event | 1.0% to 10.5% | Not reported as a range |
| Left the study entirely | 0.0% to 2.2% | Not reported as a range |
The width of those ranges is the point. A single percentage for "nausea on tirzepatide" is not a fact about the drug; it is a fact about one arm of one trial in one population at one dose. The same analysis found that nausea, diarrhoea and vomiting were the most frequent events, that most were non-serious, and that first use of an antiemetic or antidiarrhoeal was most commonly reported during dose escalation.
Individual symptoms, measured against semaglutide
SURPASS-2 is the one trial that put per-symptom rates for tirzepatide next to a comparator drug rather than next to placebo. It was open-label, ran 40 weeks in 1879 adults with type 2 diabetes, and compared tirzepatide 5 mg, 10 mg and 15 mg against semaglutide 1 mg (PMID 34170647). Rates for tirzepatide are given as a range across the three doses.
| Adverse event | Tirzepatide 5 to 15 mg | Semaglutide 1 mg |
|---|---|---|
| Nausea | 17% to 22% | 18% |
| Diarrhoea | 13% to 16% | 12% |
| Vomiting | 6% to 10% | 8% |
| Hypoglycaemia below 54 mg/dL | 0.2% to 1.7% | 0.4% |
| Serious adverse event | 5% to 7% | 3% |
This is a diabetes trial at doses and a duration that differ from the obesity trials, so the percentages should not be lifted across to Zepbound. What it does establish is that the symptom profile was broadly similar to a GLP-1 receptor agonist at a therapeutic dose, not categorically worse. We compare the two drugs on weight in semaglutide vs tirzepatide.
Why almost everything happens in the first five months
Tirzepatide starts at 2.5 mg and rises in 2.5 mg steps no sooner than every four weeks, so the top dose is not reached before week 21. SURMOUNT-1 built a 20-week escalation period into its design. Both the original trial report and the pooled analysis put the gastrointestinal events primarily in that window.
That changes how the rates above should be read. A 72-week trial reports the proportion who experienced an event at any point, which is cumulative rather than a description of week 60. Someone nauseated for a fortnight in month two counts in the same percentage as someone nauseated throughout.
Work out what the trial percentages mean for you
The weight figures in that first table are averages from SURMOUNT-1. See what they come to from your own starting weight.
Do the side effects cause the weight loss?
This is the most persistent belief about these drugs, and the pooled SURMOUNT analysis tested it directly. Weight reduction was similar among participants who reported no nausea, nausea alone, or any nausea, vomiting or diarrhoea. A mediation analysis put the contribution of those symptoms plus dyspepsia at up to 3.1% of total weight reduction (PMID 39789843).
So feeling unwell is not the mechanism, and not feeling unwell is not a sign the dose is failing. The corresponding analysis of the semaglutide trials reached the same conclusion, with under one percentage point of the additional weight loss mediated by gastrointestinal events.
Who these rates do not describe
- Excluded populations. SURMOUNT-1 excluded people with diabetes, and the SURMOUNT programme excluded a range of other conditions. Nothing in these rates describes someone the trials would not have enrolled.
- Self-reported symptoms. These events are what participants reported, in trials where 20 weeks of escalation made the treatment arm reasonably guessable.
- Long-term use. The longest of these trials ran 88 weeks. Rates beyond that are not in this evidence base.
- Compounded tirzepatide. None of these trials used a compounded product, and neither the dose accuracy nor the adverse event profile of compounded vials is described by them.
The warnings that are not in the average
Frequency tables describe what happened often. The tirzepatide label also carries risks that are rare, serious, or both, and these do not show up in a percentage from a 2500-person trial:
- A boxed warning for thyroid C-cell tumours, based on findings in rats. The relevance to humans is not established, and the drug is contraindicated in anyone with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia syndrome type 2.
- Acute pancreatitis.
- Acute gallbladder disease.
- Acute kidney injury, including cases following dehydration from vomiting or diarrhoea.
- Severe gastrointestinal disease.
- Hypersensitivity reactions, including anaphylaxis and angioedema.
- Hypoglycaemia when combined with insulin or an insulin secretagogue.
- Diabetic retinopathy complications in people with type 2 diabetes.
- Monitoring for depression, suicidal thoughts and behaviour.
In SURMOUNT-2, the type 2 diabetes trial, serious adverse events were reported by 7% of participants overall and two deaths occurred in the 10 mg group, neither considered related to study treatment by the investigator (PMID 37385275).
FAQ
What are the most common side effects of tirzepatide?
Gastrointestinal, principally nausea, diarrhoea and vomiting. Across SURMOUNT-1 to -4, between 27.8% and 72.8% of participants on tirzepatide reported at least one gastrointestinal event against 12.2% to 32.5% on placebo, and most events were mild to moderate.
How many people stop taking tirzepatide because of side effects?
In SURMOUNT-1, adverse events caused discontinuation in 4.3% on 5 mg, 7.1% on 10 mg and 6.2% on 15 mg, against 2.6% on placebo, over 72 weeks. Pooled across SURMOUNT-1 to -4, discontinuation specifically for gastrointestinal events ranged from 1.0% to 10.5%.
Are side effects worse at 15 mg than at 5 mg?
Not straightforwardly. SURMOUNT-1 recorded a higher discontinuation rate at 10 mg (7.1%) than at 15 mg (6.2%), with 5 mg lowest at 4.3%. The pooled analysis places events mainly during dose escalation rather than at any particular maintenance dose.
How long do tirzepatide side effects last?
The published tirzepatide analyses report when events occurred, primarily during the escalation period, rather than how long each one lasted, so there is no median duration to quote from them. The equivalent semaglutide analysis did report durations, and we cover those in semaglutide side effects.
Does having side effects mean tirzepatide is working?
No. Weight reduction was similar in participants who reported no nausea, nausea alone, or any nausea, vomiting or diarrhoea, and a mediation analysis attributed at most 3.1% of the total weight reduction to those symptoms.
What are the serious risks?
The label carries a boxed warning for thyroid C-cell tumours based on rat studies, contraindications in medullary thyroid carcinoma and multiple endocrine neoplasia syndrome type 2, and warnings covering pancreatitis, gallbladder disease, acute kidney injury, severe gastrointestinal disease, hypersensitivity, hypoglycaemia in combination with insulin or secretagogues, diabetic retinopathy and monitoring for suicidal thoughts.
This article reports what the published tirzepatide trials and the product label record. It is not medical advice, and nothing here is a reason to start, change or stop a dose without your prescriber. Seek medical attention for severe or persistent abdominal pain, persistent vomiting, or signs of an allergic reaction.
Sources
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). <em>N Engl J Med</em>. 2022;387(3):205-216. PMID: 35658024
- Rubino DM, Pedersen SD, Connery L, et al. Gastrointestinal tolerability and weight reduction associated with tirzepatide in adults with obesity or overweight with and without type 2 diabetes in the SURMOUNT-1 to -4 trials. <em>Diabetes Obes Metab</em>. 2025;27(4):1826-1835. PMID: 39789843
- Garvey WT, Frias JP, Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2). <em>Lancet</em>. 2023;402(10402):613-626. PMID: 37385275
- Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2). <em>N Engl J Med</em>. 2021;385(6):503-515. PMID: 34170647
- Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity (SURMOUNT-4). <em>JAMA</em>. 2024;331(1):38-48. PMID: 38078870
- Zepbound (tirzepatide) and Mounjaro (tirzepatide) United States prescribing information, Eli Lilly and Company, for the boxed warning, contraindications and warnings.