Short answer: Yes. All four US labels report indigestion (dyspepsia) and acid reflux (GERD) more often than on placebo. In the weight-loss trials, indigestion was reported by 9% on Wegovy versus 3%, and 9% to 10% on Zepbound versus 4%; reflux by 5% versus 3% and 4% to 5% versus 2%. A 2025 review of 55 trials found GLP-1 medicines probably raise the risk of reflux, by about 4 extra cases per 1,000 people.
The labels use two terms. Dyspepsia is indigestion: an upset, burning or full feeling in the upper stomach. Gastroesophageal reflux disease (GERD) is stomach acid coming back up into the food pipe, often felt as heartburn. The patient leaflets use the words "indigestion", "upset stomach" and "heartburn".
| Medicine and trials | Indigestion (dyspepsia) | Reflux (GERD) |
|---|---|---|
| Ozempic 0.5 mg and 1 mg, type 2 diabetes | 3.5% and 2.7% (placebo 1.9%) | 1.9% and 1.5% (placebo 0%) |
| Wegovy 2.4 mg, adults, weight reduction | 9% (placebo 3%) | 5% (placebo 3%) |
| Mounjaro 5, 10 and 15 mg, type 2 diabetes | 8%, 8% and 5% (placebo 3%) | 1.7%, 2.5% and 1.7% (placebo 0.4%) |
| Zepbound 5, 10 and 15 mg, weight reduction | 9%, 9% and 10% (placebo 4%) | 4%, 4% and 5% (placebo 2%) |
The Wegovy label also lists gastritis, a term that includes reflux gastritis (irritation of the stomach lining), in 4% versus 1% on placebo. In the Wegovy trial of people aged 12 and older, reflux was reported by 4% versus 2%.
The trials differ in doses, length and the people in them, so the rows are not a ranking. As with other stomach side effects, the weight-loss trials at higher doses reported more than the diabetes trials.
Chiang and colleagues pooled 55 placebo-controlled trials with 106,395 people taking GLP-1 medicines for type 2 diabetes, overweight or obesity, or fatty liver disease. They found that GLP-1 medicines probably increase the risk of reflux (risk ratio 2.19), which works out to about 4 more cases per 1,000 people than on placebo.
The increase looked larger in trials of people with overweight or obesity, with medicines that cause more weight loss, and with high-dose versions, though the authors note these subgroup differences were not statistically significant. For most other stomach and gallbladder problems they looked at, they found little or no effect, apart from gallstones.
The labels do not say why reflux happens, but they do describe how the medicines act on the stomach. The Ozempic label says semaglutide delays early stomach emptying after a meal. The Mounjaro and Zepbound labels say tirzepatide delays stomach emptying, with the delay largest after the first dose and smaller over time.
Before starting, the Ozempic, Mounjaro and Zepbound leaflets ask you to tell your provider if you have severe problems with your stomach, such as slowed stomach emptying (gastroparesis) or problems digesting food. The Mounjaro leaflet adds that stomach problems, sometimes severe, have been reported, and to tell your provider if they are severe or will not go away.
Heartburn sits in the upper stomach and chest, close to where other warnings on these labels are felt. The labels say to stop the medicine and call a provider right away for severe stomach pain that will not go away, sometimes felt through to the back (see pancreatitis), and list upper stomach pain with fever, yellow skin or eyes, or clay-colored stools as signs of gallbladder problems.
For ordinary heartburn, useful notes for your prescriber or pharmacist are when it started relative to your dose and dose changes, what time of day it comes on, how it relates to meals, and anything you took for it. Ask a pharmacist before adding an over-the-counter remedy, since the labels say these medicines can affect how other pills are absorbed (see GLP-1 medicines and other pills). Dose Track keeps side-effect notes next to each logged dose.
Read more on Dose Track: GLP-1 side effects week by week · GLP-1s before surgery and anesthesia · Ozempic side effects · Wegovy side effects · Mounjaro side effects · Zepbound side effects