Tirzepatide's side effects are well documented, because the Zepbound label pools two placebo-controlled trials in which 2,519 adults took it for up to 72 weeks. [1] Placebo groups are what make that record useful. Many people feel queasy or tired on any given week, and only the gap over placebo belongs to the drug.
How the dose climbs, and why the early weeks are the roughest, is covered in tirzepatide dosage. This page sets out what was recorded, from the common to the rare.
The common side effects, by dose
The label lists every reaction that occurred in at least 2% of people on tirzepatide and more often than on placebo [1]. The trials enrolled adults with obesity or overweight, and 25% of them also had type 2 diabetes.
| Side effect | 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% |
| Indigestion (dyspepsia) | 4% | 9% | 9% | 10% |
| Injection-site reactions | 2% | 6% | 8% | 8% |
| Fatigue | 3% | 5% | 6% | 7% |
| Hypersensitivity reactions | 3% | 5% | 5% | 5% |
| Burping | 1% | 4% | 5% | 5% |
| Hair loss | 1% | 5% | 4% | 5% |
| Acid reflux | 2% | 4% | 4% | 5% |
| Dizziness | 2% | 4% | 5% | 4% |
Two patterns stand out. Constipation was most common on the lowest dose, 17% on 5 mg against 11% on 15 mg. Most other stomach effects rose with dose, though the steps between 10 mg and 15 mg were small.
Stomach and bowel effects
Taken together, stomach and bowel reactions affected 56% of people on each of the three doses, against 30% on placebo [1]. Treatment was stopped for these reactions by 1.9%, 3.3% and 4.3% on 5, 10 and 15 mg, and by 0.5% on placebo.
The label notes that most nausea, vomiting and diarrhea occurred during dose escalation and eased over time. A pooled look at SURMOUNT-1 to 4 adds a practical detail [3]. When people needed medicine for diarrhea or nausea, they most often started it during those escalation weeks.
The label also warns of severe reactions. It does not recommend tirzepatide for people with severe gastroparesis, a condition in which the stomach empties very slowly [1].
Hair loss, injection sites and allergic reactions
Hair loss in the trials was tied to weight reduction and was far more common in women [1]. On tirzepatide it was reported by 7.1% of women and 0.5% of men. No one on tirzepatide stopped treatment because of it.
Some people develop antibodies to tirzepatide, and they had more skin reactions. Injection-site reactions occurred in 11.3% of people with anti-tirzepatide antibodies, against 1% of those without them [1].
Immediate allergic-type reactions, within a day of a dose, occurred in 2.1% on tirzepatide and 0.4% on placebo. Most were rashes or itching. Anaphylaxis and angioedema have been reported since approval, and the label says to stop the drug and seek care if they occur.
Rotating where the injection goes is one of the questions covered in peptide injection sites.
Less common but serious events
The label’s warnings section lists events that are uncommon but matter more when they occur [1]. The pooled weight trials put a number on several of them.
| Event | Tirzepatide | Placebo |
|---|---|---|
| Gallbladder inflammation (cholecystitis) | 0.7% | 0.2% |
| Gallstones (cholelithiasis) | 1.1% | 1% |
| Gallbladder removal | 0.2% | 0% |
| Acute pancreatitis, confirmed by adjudication | 0.2% | 0.2% |
| Acute kidney injury | 0.5% | 0.2% |
| Low blood pressure | 1.6% | 0.1% |
Pancreatitis looked different across programs. In the weight trials the rate matched placebo, but the sleep apnea trials recorded 0.84 cases per 100 years of exposure on tirzepatide and none on placebo [1]. The label says to stop tirzepatide if pancreatitis is suspected.
The label ties kidney injury to fluid loss from vomiting and diarrhea, and advises monitoring kidney function in people with those symptoms. Low blood pressure was more frequent in people already taking blood pressure medicine, 2.2% against 1.2%.
Low blood sugar is mainly a risk alongside insulin or sulfonylureas. In the trial of people with type 2 diabetes, glucose below 54 mg/dL was reported in 4.2% on tirzepatide and 1.3% on placebo. Heart rate rose by a mean of 1 to 3 beats per minute.
Reports since approval
Postmarketing reports come from voluntary reporting, so they show what can happen, not how often [1]. The label lists pancreatitis, including severe and fatal forms, and bowel obstruction. It also lists severe constipation, anaphylaxis, and kidney failure that sometimes required dialysis.
One risk surfaces around surgery. Aspiration of stomach contents under anesthesia or deep sedation has been reported with drugs in this class, so the label asks patients to tell their care team about planned procedures.
The label’s change log also records a removal. Suicidal behavior and ideation was dropped from the warnings section in February 2026 [1].
How often people stop
In SURMOUNT-1, the largest single trial, 2,539 adults without diabetes took tirzepatide or placebo for 72 weeks. [2] Most adverse events were stomach-related and mild to moderate, and they occurred mainly while the dose was being raised.
Across the label’s two pooled trials, adverse reactions ended treatment for 4.8%, 6.3% and 6.7% of people on 5, 10 and 15 mg, against 3.4% on placebo [1]. Most of those stops came in the first few months.
A 2025 meta-analysis of phase 1 to 3 trials found adverse events more likely on tirzepatide than placebo, with an odds ratio of 1.34 [4]. Serious adverse events did not differ, and stopping for side effects was more likely at higher doses.
What this means
The record is dominated by stomach and bowel effects that are common, dose-linked and mostly early. The serious events are uncommon, but the label names symptoms for each one, and those deserve a call to a prescriber.
Whether semaglutide carries a lighter burden is taken up in tirzepatide vs semaglutide. The wider question of how peptide safety depends on the compound and its source is in are peptides safe. Other options for weight sit on the weight goal page.