GLP-1 side effects, by how often the trials reported them
Nausea is the one everybody has heard about, and the trials bear it out: 44% on semaglutide 2.4 mg against 16% on placebo, and 29% on tirzepatide 10 mg against 8%. What gets lost is everything underneath that — constipation at 24%, hair loss at 3%, and a discontinuation rate for side effects of 6.8% against 3.2% on placebo. These are the labels' own tables, not a summary of them.
What this comes down to
- On semaglutide 2.4 mg the four commonest reactions were nausea 44%, diarrhea 30%, vomiting 24% and constipation 24%, each against a placebo rate the table prints beside it.
- On tirzepatide the same reactions run lower and flatter across 5, 10 and 15 mg: nausea 25% to 29%, diarrhea 19% to 23%, vomiting 8% to 13%.
- Severe gastrointestinal reactions were reported in 4.1% of semaglutide-injection patients against 0.9% on placebo, and the product is not recommended in severe gastroparesis.
- At the newer 7.2 mg semaglutide dose, dysesthesia — altered skin sensation — was reported by 22% against 6% at 2.4 mg and 0% on placebo.
Semaglutide 2.4 mg, as the label reports it
This table is the pooled safety population from three randomized, double-blind, placebo-controlled trials in adults with obesity or overweight — 2,116 patients on semaglutide injection for up to 68 weeks against 1,261 on placebo. Every row met the label's threshold of at least 2% and more often than placebo[1].
| Reaction | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Nausea | 44% | 16% |
| Diarrhea | 30% | 16% |
| Vomiting | 24% | 6% |
| Constipation | 24% | 11% |
| Abdominal pain | 20% | 10% |
| Headache | 14% | 10% |
| Fatigue | 11% | 5% |
| Dyspepsia | 9% | 3% |
| Dizziness | 8% | 4% |
| Eructation | 7% | less than 1% |
| Gastroesophageal reflux disease | 5% | 3% |
| Hair loss | 3% | 1% |
Adverse reactions at 2% or more and greater than placebo, semaglutide injection 2.4 mg once weekly
Of patients on semaglutide injection, 6.8% stopped treatment permanently because of an adverse reaction, against 3.2% on placebo. The reactions most often behind that were nausea at 1.8% against 0.2%, vomiting at 1.2% against 0%, and diarrhea at 0.7% against 0.1%. In the separate cardiovascular outcomes trial, where 8,803 patients took the drug for a median of 37.3 months, 16% discontinued for an adverse event against 8% on placebo — a longer exposure and a higher number, which is worth holding next to the 68-week figure rather than instead of it.
The phase 3 trial behind those figures, which randomized 1,961 adults 2:1 for 68 weeks, describes nausea and diarrhea as the most common adverse events with semaglutide and adds that they were typically transient, mild to moderate, and subsided with time[4]. That qualifier is real and it's also an average. A table reporting 44% is telling you how many people had the reaction at some point. It isn't telling you how many had it every week.
Tirzepatide, across three doses
The tirzepatide table is built from two placebo-controlled weight-reduction trials and reports each dose separately, which is more useful than a pooled figure because it shows how little the rate moves between 5 mg and 15 mg[2].
| Reaction | Placebo | 5 mg | 10 mg | 15 mg |
|---|---|---|---|---|
| Nausea | 8% | 25% | 29% | 28% |
| Diarrhea | 8% | 19% | 21% | 23% |
| Vomiting | 2% | 8% | 11% | 13% |
| Constipation | 5% | 17% | 14% | 11% |
| Abdominal pain | 5% | 9% | 9% | 10% |
| Dyspepsia | 4% | 9% | 9% | 10% |
| Injection site reactions | 2% | 6% | 8% | 8% |
| Fatigue | 3% | 5% | 6% | 7% |
| Hair loss | 1% | 5% | 4% | 5% |
| Dizziness | 2% | 4% | 5% | 4% |
Adverse reactions at 2% or more and greater than placebo, tirzepatide once weekly
Taken as a whole rather than reaction by reaction, gastrointestinal adverse reactions occurred in 56% of patients at every tirzepatide dose against 30% on placebo. Discontinuation for a gastrointestinal reaction ran 1.9%, 3.3% and 4.3% at 5, 10 and 15 mg. In the 72-week trial behind the approval, adverse events caused discontinuation in 4.3%, 7.1% and 6.2% of the three dose groups against 2.6% on placebo[3].
At the higher semaglutide dose studied in two 72-week trials, nausea rose modestly — 39% against 35% at 2.4 mg and 13% on placebo — but dysesthesia, which the label defines to include paresthesia, burning sensation, allodynia and skin sensitivity, was reported by 22% against 6% at 2.4 mg and 0% on placebo. A row that goes from nothing to more than one in five is the kind of dose-related signal that is easy to miss in a summary that only looks at nausea.
The reactions the labels lead with, which aren't the common ones
Frequency and seriousness are different axes, and it's the second one the labels open with. Both carry a boxed warning about thyroid C-cell tumors in rodents and a contraindication in personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Both then list, in warnings and precautions, acute pancreatitis, acute gallbladder disease, acute kidney injury from volume depletion, severe gastrointestinal reactions, hypersensitivity including anaphylaxis and angioedema, hypoglycemia, diabetic retinopathy complications in type 2 diabetes, heart rate increase, and pulmonary aspiration during general anesthesia or deep sedation[1][2].
The anesthesia one is the newest, it's the most actionable before a planned procedure, and it follows from delayed gastric emptying. The research base there is real but young relative to the drugs it is compared against.
PubMed, via the E-utilities API
(semaglutide[tiab] OR tirzepatide[tiab]) AND (gastroparesis[tiab] OR "delayed gastric emptying"[tiab] OR aspiration[tiab])
Returned 130. Positive control — opioids, identical filter — returned 365 through the identical filter in the same session.
Opioids are the control because they are the older drug class with the same mechanism-level concern and a literature nearly three times the size. One hundred and thirty isn't a thin record for a drug class this young, and it is the reason the warning is on the label at all.
Every figure above comes from trials of the approved products at label doses with a supervised escalation schedule. No compounded product has been through a randomized trial, so none of these tables describes one. The FDA says many of the adverse events reported for compounded products appear consistent with those of the approved versions, and in the same breath that such reports are likely underreported[5].
What is otherwise known about compounded products comes from adverse event reports and two laboratory studies, both covered in the impurities article, and from the FDA's own reports of doses prescribed beyond the label, covered in the dosing article.
What the frequency tables do not settle
Three questions come off these tables and each has its own evidence. Whether nausea can be managed, and what has actually been tested for it, is in the nausea article. What the weight being lost is made of is in the lean mass article. And what happens when the drug stops is in the withdrawal trials. Which company you buy from doesn't change the pharmacology and changes a great deal of the price, which is the roster's job.
Questions people actually ask
How common is nausea on semaglutide?
The approved label reports nausea in 44% of patients on 2.4 mg once weekly against 16% on placebo, pooled across three randomized placebo-controlled weight-reduction trials totaling 2,116 patients on drug. Nausea was the single commonest reason for permanently stopping treatment, at 1.8% against 0.2% on placebo.
Is tirzepatide easier to tolerate than semaglutide?
The label tables aren't a head-to-head comparison and can't be read as one — different trials, different populations, different escalation schedules. What they show is nausea at 25% to 29% across tirzepatide doses against 44% on semaglutide 2.4 mg in its own trials. Only a randomized comparison could settle the question, and these tables aren't it.
Do GLP-1 drugs cause hair loss?
Both labels list it. Semaglutide injection reports hair loss in 3% of patients against 1% on placebo at 2.4 mg, and 6% against 1% at the 7.2 mg dose. Tirzepatide reports 4% to 5% against 1%. Rapid weight loss from any cause is associated with telogen effluvium, and the trials don't separate the two explanations.
Why do the labels warn about anesthesia?
Because these drugs slow gastric emptying, which can leave stomach contents present when a procedure assumes an empty stomach, raising the risk of pulmonary aspiration under general anesthesia or deep sedation. Both labels instruct patients to tell health care providers before a planned surgery or procedure.
Sources
Every source here was fetched and read for this article, with the identifier taken off the record that came back and the claim it supports written down beside it. All of it was read in September 2026, the same session the rest of this page draws on.
- 1.WEGOVY (semaglutide) injection, solution; WEGOVY (semaglutide) tablet — prescribing information. Novo Nordisk, via the DailyMed Structured Product Labeling service, 2026. Source · Document dated June 2026Table 3 adverse reactions at 2% or more and greater than placebo in 2,116 adults on semaglutide injection 2.4 mg against 1,261 on placebo; 6.8% versus 3.2% permanent discontinuation for adverse reactions with nausea 1.8% versus 0.2%, vomiting 1.2% versus 0% and diarrhea 0.7% versus 0.1%; 16% versus 8% discontinuation in the cardiovascular outcomes trial of 8,803 patients over a median 37.3 months; Table 4 adverse reactions at 7.2 mg including nausea 39% and dysesthesia 22%; severe gastrointestinal reactions 4.1% versus 0.9%; the boxed thyroid C-cell warning and the warnings and precautions list.
- 2.ZEPBOUND (tirzepatide) injection — prescribing information. Eli Lilly and Company, via the openFDA label API, 2026. Source · Document dated August 2026Table 1 adverse reactions at 2% or more and greater than placebo across tirzepatide 5, 10 and 15 mg against placebo; gastrointestinal adverse reactions in 56% at each dose against 30% on placebo; discontinuation for gastrointestinal reactions at 1.9%, 3.3% and 4.3%; and the boxed warning and warnings and precautions list.
- 3.Tirzepatide Once Weekly for the Treatment of Obesity. The New England Journal of Medicine, 2022. PMID 35658024 · doi:10.1056/NEJMoa2206038The 72-week phase 3 trial of 2,539 adults randomized to tirzepatide 5, 10 or 15 mg or placebo, in which adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2% and 2.6% of participants respectively, and in which the most common adverse events were gastrointestinal, mostly mild to moderate and occurring primarily during dose escalation.
- 4.Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine, 2021. PMID 33567185 · doi:10.1056/NEJMoa2032183The 68-week trial of 1,961 adults randomized 2:1 to semaglutide 2.4 mg or placebo, and its report that nausea and diarrhea were the most common adverse events with semaglutide, typically transient and mild to moderate and subsiding with time.
- 5.FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. U.S. Food and Drug Administration, 2026. Source · Document dated September 2026Adverse event reports relating to compounded semaglutide and tirzepatide prescribed at doses beyond the approved label, with symptoms including nausea, vomiting, diarrhea, abdominal pain and constipation, and the statement that such reports are likely underreported.
Key figures