Mostly gut, mostly early, and mostly during dose increases. In the largest obesity trial of tirzepatide, the drug in Mounjaro and Zepbound, nausea ran from 24.6% at the lowest dose to 33.3% at the middle one, against 9.5% on placebo, and between 4.3% and 7.1% of people stopped because of side effects.1
The serious ones are rare, specific, and listed on the label: pancreatitis, gallbladder disease, kidney injury from fluid loss, and a boxed warning about thyroid tumours in rodents.2
If you have just moved up a dose and feel awful, that is the most common version of this, and it usually settles within a week or two at the new dose. If you cannot keep fluids down, or you have severe pain that will not ease, skip to the end of this page.
What changes for most people reading this is not the molecule. It is that the trial numbers come from a setting with a fixed escalation schedule, a known concentration, and somebody checking on you. None of that applies to a vial bought online.
The scale of the gap, from our library and capture:3
- 29 GLP-1 class compounds tracked, of which 9 are approved somewhere
- 20 are not approved anywhere, including retatrutide, survodutide and amycretin
- 902 listings for those compounds across 125 sellers
- 0 of them come with a prescriber, an escalation schedule or a monitoring plan
One of the nine is not even a peptide: Foundayo, the oral member of the class, is a small-molecule pill.
How common are the common ones?
Dose-dependent. That pattern matters more than any single figure.
| Side effect, at 72 weeks | Tirzepatide 5 mg | 10 mg | 15 mg | Placebo |
|---|---|---|---|---|
| Nausea | 24.6% | 33.3% | 31.0% | 9.5% |
| Diarrhoea | 18.7% | 21.2% | 23.0% | 7.3% |
| Constipation | 16.8% | 17.1% | 11.7% | 5.8% |
| Vomiting | 8.3% | 10.7% | 12.2% | 1.7% |
| Stopped because of side effects | 4.3% | 7.1% | 6.2% | 2.6% |
From SURMOUNT-1, 2,539 adults.1
Two things to take from that table. Side effects rise with dose but not neatly, and the placebo column is not zero, which means a share of what people experience is not the drug.
For semaglutide, the drug in Ozempic and Wegovy, the pattern is the same and the headline numbers are higher. In STEP 1, which ran 1,961 adults for 68 weeks, nausea affected 44.2% on semaglutide 2.4 mg against 17.4% on placebo, 7.0% stopped because of adverse events against 3.1%, and serious adverse events occurred in 9.8% against 6.4%.4
One figure from that trial is worth holding onto: 89.7% of people on semaglutide reported some adverse event, and so did 86.4% of people on placebo. Cross-trial comparisons are unreliable because populations and escalation schedules differ, so the useful comparison is always each drug against its own placebo arm.
The two on the label that nobody lists
Both are in the approved labelling and neither appears in most side effect round-ups.
Abnormal skin sensation. Dysesthesia is listed on the Wegovy label among adverse reactions occurring in 5% or more of patients, with a dedicated subsection reporting 4.9% on the tablet form against none on placebo, covering sensitive skin, hyperesthesia, paresthesia, allodynia and skin burning sensation. The label states the incidence rose with dose and with drug levels in the blood.6
The Zepbound label carries it too, at 0.2%, 0.2% and 0.4% across its three doses against 0.1% on placebo.7
So it is a class effect at very different rates: roughly one in 250 on tirzepatide, one in twenty on semaglutide tablets, and far higher on retatrutide, which our skin sensitivity guide covers in full.
Raised resting heart rate. The Wegovy label gives this its own Warnings and Precautions section, which puts it in a different category from the adverse reactions table. Mean increases ran 1 to 4 beats per minute against placebo, and the label instructs clinicians to monitor heart rate and to discontinue on a sustained increase.6
Averages hide the spread. In the adult weight trials, 41% of people on the drug had a maximum rise of 10 to 19 bpm at some visit against 34% on placebo, and 26% had a rise of 20 bpm or more against 16%.6 The Mounjaro label reports 2 to 4 bpm against a 1 bpm rise on placebo, and records episodes of sinus tachycardia with increases of 15 bpm or more.8
Our guide on resting heart rate covers what to do about a number climbing on a watch, including the part most people get wrong, which is that a single reading tells you almost nothing.
The ones nobody warns you about
Milder than the headline effects, and all of them are in the label's own adverse reactions table.2
| At 5, 10 and 15 mg of tirzepatide | Placebo |
|---|---|
| Dyspepsia, 9% to 10% | 4% |
| Fatigue, 5% to 7% | 3% |
| Eructation, the burping, 4% to 5% | 1% |
| Hair loss, around 4% to 5% | lower |
| Reflux, around 4% to 5% | lower |
Burping is the one people search hardest for, often described as sulfurous, and it is a real labelled effect at 4% to 5% against 1% on placebo. Food moving more slowly through the stomach is the plausible mechanism, and it eases at a steady dose.
Fatigue runs 5% to 7% against 3% on placebo on the Zepbound label, and 11% against 5% on Wegovy.67 The placebo column is the part to notice: a good share of this is not the drug. Our fatigue guide covers why the day after a dose is the one people report, and the four causes that are not the injection. Eating considerably less produces the same thing on its own.
Hair loss is on the tirzepatide label and is not on the semaglutide one. Rapid weight loss is itself a recognised trigger for temporary shedding, which happens after bariatric surgery and after any sharp caloric drop, and it usually reverses.
Reflux and heartburn follow the same slowed-emptying mechanism, and are worse lying down soon after eating.
None of these is dangerous. They are a common reason people stop early, which matters more than their severity suggests.
How long do GLP-1 side effects last?
Weeks rather than months for most people, and they fade once the dose stops moving.
Gut effects cluster around dose increases instead of spreading evenly across treatment. In trials, most first episodes of nausea, vomiting or diarrhoea appeared in the first four weeks at a given dose, and few new cases appeared once someone had been at that dose a while.
So if you felt fine for a month and then felt terrible, check what changed. It is usually the dose. If nothing changed and you suddenly feel much worse, that is a different question and the end of this page covers it.
That pattern is also why the escalation schedule exists, and why going up faster than the label is the one decision most likely to make you ill.
What are the serious side effects?
Uncommon, specific, and each with symptoms you should be able to recognise.2
Thyroid C-cell tumours. This is the boxed warning, the strongest kind. Semaglutide causes thyroid C-cell tumours in rodents at clinically relevant exposures. Whether it does so in humans is unknown, and the labels say exactly that. It is contraindicated in anyone with a personal or family history of medullary thyroid carcinoma or MEN 2.
Acute pancreatitis. Observed with GLP-1 receptor agonists, and the label instruction is to stop if it is suspected. What you would notice is severe abdominal pain that persists, often going through to your back.
Acute gallbladder disease. Occurred in trials. Rapid weight loss raises gallstone risk independently of any drug, which makes this hard to attribute and serious either way.
Acute kidney injury from fluid loss. Reported after approval, mostly in people who became dehydrated through vomiting or diarrhoea rather than through anything the drug did directly. Our dehydration guide covers that path in detail, because it is the one that starts as something minor.
Pulmonary aspiration under anaesthesia. Added to the semaglutide label in January 2025. These drugs delay stomach emptying, so a stomach assumed empty before sedation may not be. Our surgery guide covers what to tell an anaesthetist.
Severe gut reactions have their own section in both labels, with numbers attached. In the pooled tirzepatide trials, severe gastrointestinal reactions were reported by 1.7% at 5 mg, 2.5% at 10 mg and 3.1% at 15 mg, against 1.0% on placebo, and discontinuation specifically for gut effects ran 1.9%, 3.3% and 4.3% against 0.5%.2 Section 5.7 of the Ozempic label, revised in 2025, adds that it is not recommended in patients with severe gastroparesis.
And in June 2025 the European regulator concluded that NAION, a form of sudden vision loss, is a very rare side effect of semaglutide medicines, meaning it may affect up to 1 in 10,000 people taking them. Large observational studies suggested roughly a twofold increase in risk, which the regulator translated into about one additional case per 10,000 person-years. Its instruction is to stop semaglutide if NAION is confirmed.5 The manufacturer's position is that the data do not establish causation.
Is a grey-market vial riskier than a prescription?
Yes, and not because the molecule differs. The trial numbers cannot tell you this part.
Nobody enforces the escalation schedule. The trial rates above come from people who climbed the ladder over 20 weeks. Starting higher, or climbing faster, moves you up the dose column without the adaptation that made those rates tolerable.
You may not know the concentration. A dosing error of a few units is a small percentage at a full dose and a large one at a low dose, and a vial's actual content is not something you can verify. Our guide on dose calculation errors covers the arithmetic that catches it.
Nobody is monitoring. The label instructions assume someone checks kidney function when you report severe vomiting, and adjusts insulin or sulfonylureas to avoid hypoglycaemia. Outside that system, nobody does either unless you ask.
Twenty of the 29 GLP-1 class compounds we track have no label at all, and they are not niche: those twenty carry 902 listings across 125 of the 151 sellers we follow.5 For retatrutide there is phase 2 data. For survodutide, amycretin and several others there is less, and the side effect profile quoted on a product page is extrapolated from a molecule that was actually tested.
What about muscle loss, your face, and your mood?
Three things people worry about that the warnings section does not cover, because they are consequences of losing weight rather than properties of the drug.
Muscle loss. Real and measured. In trials, lean tissue accounted for roughly 30 to 40% of total weight lost, which is in line with weight loss by other means. Our guide on what happens after significant weight loss covers what preserves it, and it is not sold in a vial.
Facial volume. Losing fat means losing facial fat. The drug is the reason you are losing weight rather than a separate cause of the appearance.
Mood changes. The most contested of the three. Regulators reviewed a suicidality signal and did not find a causal link. A separate question, blunted motivation or flattened affect, has no surveillance data behind it at all, and our piece on that covers why the mechanism is plausible and the evidence absent.
Which is easier to tolerate?
Less decisive than the marketing on either side.
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Nausea, headline trial figure | 44.2% at 2.4 mg | 24.6% to 33.3% by dose | no comparable figure exists |
| Stopped for side effects | 7.0% | 4.3% to 7.1% by dose | no comparable figure exists |
| Label warnings | full set, boxed | full set, boxed | none, because no label exists |
| Trial length behind it | 68 weeks | 72 weeks | 48 weeks, phase 2 only |
Head-to-head data is thin and the populations differ, so read the first row as within-drug, not between-drug.14 What is not ambiguous is the last row: two of these have been through full approval programmes and one has not.
When to stop and get seen
Not the ordinary nausea, which is expected. These:
Severe abdominal pain that persists, especially radiating to the back. Vomiting you cannot stop for a day. Passing very little urine, or feeling faint on standing. Sudden vision changes. Signs of gallbladder trouble: pain in the upper right abdomen, fever, yellowing of the skin or eyes.
And one that is not an emergency but needs saying: if you are having surgery or any procedure with sedation, tell them you are on this drug, whatever you are on and wherever it came from.
Common questions
What are the most common side effects of GLP-1 drugs?
Nausea, diarrhoea, constipation and vomiting, in that order. In SURMOUNT-1, nausea affected 24.6% to 33.3% of tirzepatide users depending on dose, against 9.5% on placebo. Across the semaglutide trials nausea ran around 44% at the 2.4 mg dose.
I increased my dose three days ago and feel awful. Is that normal?
That is the most common pattern. In trials, most first episodes of nausea, vomiting and diarrhoea appeared within the first four weeks at a new dose and settled while the dose held steady. What is not routine is being unable to keep fluids down for a day, severe pain that will not ease, or passing very little urine.
Do GLP-1 drugs cause skin sensitivity?
Yes, and it is on both approved labels. Wegovy lists dysesthesia among adverse reactions at 5% or more, with 4.9% reported on the tablet form against none on placebo. Zepbound reports 0.2% to 0.4% by dose against 0.1%. Rates are far higher on retatrutide.
Do they raise your heart rate?
Yes, by 1 to 4 beats per minute on average, and the Wegovy label gives it a dedicated warnings section instructing clinicians to monitor and to discontinue on a sustained increase. Larger single readings are common: 26% of treated adults had a rise of 20 bpm or more at some visit, against 16% on placebo.
How long do GLP-1 side effects last?
Most appear in the first few weeks at a given dose and settle at a steady dose. They tend to return at the next increase, which is why they cluster around escalation instead of spreading evenly.
Are the serious side effects common?
No. Pancreatitis, gallbladder disease, kidney injury and the thyroid signal are all uncommon, and all are on the label with instructions to stop and seek care. The boxed warning about thyroid tumours comes from rodent studies, and the labels state that human relevance is unknown.
Is tirzepatide easier to tolerate than semaglutide?
Trial figures suggest fewer gut effects for tirzepatide, but the populations and escalation schedules differ enough that cross-trial comparison is unreliable. Each drug against its own placebo arm is the honest comparison.
What are the side effects of retatrutide?
Mostly unknown at this point. There is phase 2 data showing dose-related gut effects and no label, because it is not approved anywhere. Anything stated with confidence about its side effect profile is extrapolated from drugs that have been through more testing.
Why am I burping so much, and why does it smell like sulfur?
Eructation is on the tirzepatide label at 4% to 5% depending on dose, against 1% on placebo. Food moving more slowly through the stomach is the plausible mechanism. It is not dangerous and usually eases once the dose holds steady.
Does tirzepatide cause hair loss?
Hair loss is listed in the tirzepatide label's common adverse reactions, at roughly 4% to 5%, and it is not listed on the semaglutide label. Rapid weight loss by any means is a recognised trigger for temporary shedding, so attribution is difficult, and it usually reverses.
Do GLP-1 side effects go away?
For most people the gut effects settle within a few weeks at a steady dose, and return at the next increase. The ones tied to weight loss itself, like fatigue or hair thinning, follow the rate of loss rather than the dose.
Do side effects mean it is working?
No. The placebo arms of these trials reported nausea too, and people who tolerate the drug well still lose weight. Severity of side effects is not a dose gauge or a progress marker.
Can I avoid the nausea by taking less?
Lower doses do produce fewer gut effects in every trial of both drugs, and they also produce less weight loss. Our microdosing guide covers what is actually known about dosing below the label.
What should I tell a doctor before surgery?
That you are taking it, which drug, when you last injected and at what dose. These drugs delay stomach emptying and the semaglutide label now carries a warning about aspiration under anaesthesia.
Sources
- Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine 2022;387:205-216. doi:10.1056/NEJMoa2206038. Phase 3 trial, 2,539 adults, 72 weeks including 20 weeks of escalation. Source for the adverse event rates by dose and the discontinuation figures, read via the published results and the sponsor's results announcement, which agree.
- Wegovy and Ozempic prescribing information, Warnings and Precautions, revisions of January and October 2025. accessdata.fda.gov. The approved labels. Boxed warning for thyroid C-cell tumours in rodents with human relevance undetermined; warnings covering acute pancreatitis, acute gallbladder disease, acute kidney injury due to volume depletion, hypoglycaemia with concomitant insulin or secretagogues, diabetic retinopathy complications, hypersensitivity, severe gastrointestinal reactions, and pulmonary aspiration during general anaesthesia or deep sedation, the last added in January 2025. Section 5.7 states that the drug is not recommended in patients with severe gastroparesis, language that was not in the label before 2025. Also the source for the tirzepatide adverse reaction table pooled from SURMOUNT-1 and SURMOUNT-2: dyspepsia 9 to 10% against 4% on placebo, fatigue 5 to 7% against 3%, eructation 4 to 5% against 1%, with hair loss and gastro-oesophageal reflux among the reactions reported in at least 5% of patients; severe gastrointestinal reactions 1.7%, 2.5% and 3.1% by dose against 1.0%, and discontinuation for gastrointestinal reactions 1.9%, 3.3% and 4.3% against 0.5%.
- Peptide Decoding compound library and vendor price capture, 29 September 2026. peptidedecoding.com/prices. Our own data, counting one priced product at one seller as a listing. 29 compounds in the library act on GLP-1, GIP, glucagon or amylin receptors; 9 are approved somewhere and 20 are not; those compounds carry 902 listings across 125 sellers.
- Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine 2021;384:989-1002. doi:10.1056/NEJMoa2032183. Phase 3 trial, 1,961 adults, 68 weeks. Nausea 44.2% against 17.4% on placebo; adverse events leading to discontinuation 7.0% against 3.1%; discontinuation specifically for gastrointestinal events 4.5% against 0.8%; serious adverse events 9.8% against 6.4%; any adverse event 89.7% against 86.4%. Read via the published trial report and the American College of Cardiology summary, which agree.
- European Medicines Agency, Pharmacovigilance Risk Assessment Committee. PRAC concludes eye condition NAION is a very rare side effect of semaglutide medicines, 6 June 2025. ema.europa.eu. The regulator's own statement. Concludes NAION may affect up to 1 in 10,000 people taking semaglutide, that epidemiological studies suggest roughly a twofold increase in risk in adults with type 2 diabetes, that this corresponds to about one additional case per 10,000 person-years, and that treatment should stop if NAION is confirmed. The WHO issued a related alert on 27 June 2025.
- Wegovy (semaglutide) prescribing information. accessdata.fda.gov. The approved label. Dysesthesia listed among adverse reactions occurring in 5% or more of patients, with a subsection reporting 4.9% on the tablet form against none on placebo, preferred terms including sensitive skin, hyperesthesia, paresthesia, allodynia and skin burning sensation, and the statement that incidence increased with increasing dosage and drug levels in the blood. Section 5.9, Heart Rate Increase: mean increases of 1 to 4 beats per minute against placebo, with maximum changes from baseline of 10 to 19 bpm in 41% of treated adults against 34% on placebo and of 20 bpm or more in 26% against 16%; clinicians instructed to monitor heart rate and to discontinue on a sustained increase. Fatigue reported in 11% against 5% on placebo.
- Zepbound (tirzepatide) prescribing information, Adverse Reactions, section 6.1. pi.lilly.com. The approved label. Dysesthesia reported at 0.2%, 0.2% and 0.4% at 5, 10 and 15 mg against 0.1% on placebo. Fatigue at 5%, 6% and 7% by dose against 3% on placebo, pooled across the two weight-management trials.
- Mounjaro (tirzepatide) prescribing information, Adverse Reactions, Heart Rate Increase. accessdata.fda.gov. The approved label. Mean heart rate increase of 2 to 4 beats per minute against a mean increase of 1 beat per minute on placebo. Episodes of sinus tachycardia, associated with a concomitant increase from baseline of 15 beats per minute or more, were also reported. The label states that the clinical relevance of heart rate increases is uncertain.
Citing this page. Peptide Decoding. What Are the Side Effects of GLP-1 Peptides? Trial rates from SURMOUNT-1, label warnings as of the 2025 revisions, library figures from the 29 September 2026 capture. https://peptidedecoding.com/guides/glp-1-side-effects