Glucagon-like peptide-1 (GLP-1) receptor agonists have revolutionized the treatment of type 2 diabetes and obesity. However, for many users, the benefits of weight loss and blood sugar management come with gastrointestinal (GI) issues. While these symptoms are often temporary, understanding why they happen and how to ease them is key to staying on track with your treatment.

GLP-1 is a hormone naturally produced in your intestines in response to food. GLP-1 medications mimic this hormone, but they last much longer in the body.

The gut impact of GLP-1s involves several mechanisms:

  • Delayed gastric (stomach) emptying: GLP-1s slow down the rate at which food leaves your stomach. This helps you feel full longer but can lead to feelings of heaviness or nausea.
  • The gut-brain axis: These drugs interact with the area postrema in the brainstem (the region that controls the vomiting reflex) to reduce appetite, which can sometimes trigger nausea.
  • Intestinal motility: GLP-1s can influence how quickly (or slowly) waste moves through the intestines, affecting bowel habits.

Most people starting a GLP-1 medication will experience at least one mild to moderate GI symptom. According to clinical data, these are the most common issues:

  • Nausea: Reported by up to 44% of users in some trials, often occurring shortly after an injection or dose increase.
  • Vomiting: Usually linked to eating too quickly or consuming high fat meals while on the medication.
  • Diarrhea: Often occurs as the body adjusts to the changes in intestinal transit time.
  • Constipation: Because the medication slows digestion, waste may stay in the colon longer, leading to harder stools.
  • Abdominal pain and bloating: Frequently caused by the buildup of gas or slow moving food.
  • Acid reflux (heartburn): Slower stomach emptying can cause stomach acid to back up into the esophagus.

Yes, semaglutide (the active ingredient in Ozempic, Wegovy, Rybelsus, and other GLP-1 drugs) is well-known for causing GI side effects. In clinical trials for Wegovy, nearly half of the participants reported nausea. These symptoms are typically dose-dependent, meaning they are most intense when you first start the medication or when your doctor increases your dosage.

While individual reactions vary, research and meta-analyses suggest some differences in how various GLP-1s affect your GI system.

Dulaglutide (Trulicity) is sometimes noted in comparative studies for having a slightly lower risk of severe nausea and diarrhea compared to high-dose semaglutide or tirzepatide.

Long-acting versions (taken once weekly) provide a steady level of the drug, which can lead to more persistent but milder symptoms for some people. Short-acting versions (taken daily) may cause sharper peaks in nausea but might be cleared from the system faster.

Ultimately, the best GLP-1 is the one that works for your specific metabolic needs, managed through a careful titration (slow dose increase) schedule.

If you are struggling with “GLP-1 stomach,” you don’t necessarily have to stop the medication. Many people find relief by adjusting their habits.

Low and slow titration

The most effective way to prevent GI issues is to start at the lowest possible dose and increase it very slowly. If a dose increase makes you sick, talk to your doctor about staying at the current dose for an extra month to let your body get used to the medication.

Modify your eating habits

  • Eat smaller, more frequent meals: Don’t try to eat “normal” portions. Stop eating the moment you feel a “sigh” of fullness.
  • Avoid triggers: High fat, greasy, and spicy foods are significantly harder to digest and are the primary triggers for vomiting and reflux.
  • Bland is better: Follow the BRAT diet (bananas, rice, applesauce, toast) during particularly nauseous days.
  • Try a natural nausea remedy: Eat a small piece of fresh or candied ginger, or drink ginger tea, chamomile tea, or peppermint tea.

Stay hydrated and upright

  • Sip, don’t gulp: Drink water throughout the day to avoid dehydration, which can worsen nausea and lead to kidney issues.
  • Post-meal movement: Stay upright for at least 30 to 60 minutes after eating to help gravity assist your slowed digestion.

While mild nausea is normal, severe or persistent abdominal pain can be a sign of a rare but serious complication like pancreatitis or a gallbladder issue. If you experience intense pain that radiates to your back, seek medical attention immediately.

While GI side effects are a common part of the GLP-1 journey, they are usually manageable and often subside as your body adapts to the medication. By increasing your dose slowly over time (under your doctor’s guidance), staying hydrated, and adjusting your eating habits, you can successfully minimize discomfort while achieving your long-term health goals.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.