Why do semaglutide and tirzepatide cause nausea and stomach pain?

The exact mechanism by which semaglutide and tirzepatide cause digestive symptoms like nausea and stomach pain is unclear, but it is thought that they are caused by effects on the central nervous system, delayed stomach emptying, altered intestinal motility, and/or buildup of acids in the intestine. These mechanisms are intended to help control appetite and weight, but they can also result in nausea and stomach pain.

How long does nausea last with semaglutide and tirzepatide?

Nausea is common when first starting semaglutide and tirzepatide and/or during dose escalation, but it is usually overcome within a few months once you are on a stable dose. If you are still experiencing bothersome nausea after this time and are making sure to eat small, frequent meals, then you may need to discuss with your Aayu Well doctor whether this is the right medication for you.

How can I get relief from nausea due to semaglutide and tirzepatide?

Nausea may occur when your body is getting used to these medications. To minimize nausea when taking these medications, consider the following strategies:

• Dose: Increase the dose of semaglutide and tirzepatide slowly (for subcutaneous semaglutide, this is typically done in 4-week intervals starting at 0.25mg). Follow the directions written on your prescription carefully. Your experienced care team at Aayu Well will be following you closely to adjust your dose appropriately.
• Timing: Be sure to take your medication once a week, and not sooner.
• Diet: Eat smaller, more frequent meals throughout the day. Avoid high-fat and spicy foods.
• Hydration: Drink plenty of fluids throughout the day but avoid drinking large amounts of liquid with your meals, since this can increase feelings of fullness and discomfort. Ginger tea can also help alleviate nausea.
• Lifestyle: Avoid lying down immediately after eating. Instead, stay upright to reduce the risk of acid reflux.

Implementing these tips can help reduce the nausea associated with semaglutide and tirzepatide. Your Aayu Well doctor will recommend a personalized strategy to help you deal with any nausea from these medications.

Lastly, if you are still experiencing nausea, especially at higher doses of semaglutide and tirzepatide, you may consider taking anti-nausea medications like ondansetron (see below).

Can you take ondansetron (Zofran) with semaglutide or tirzepatide?

Ondansetron (Zofran) is a medication that helps with nausea. It has been effective for some patients who experience nausea from semaglutide and tirzepatide. This medication requires a prescription from your Aayu Well Medical doctor, who will determine if it is safe for you to take.

What to do if you get vomiting from semaglutide or tirzepatide?

If you develop vomiting from semaglutide or tirzepatide, you should inform your Aayu Well doctor. You may need to increase your dosage more slowly and/or eat smaller, more frequent meals. It is important to take it easy, stay hydrated, avoid strong odors and triggers, and eat bland foods. If you are having any severe symptoms (for example severe abdominal pain and/or headache, infrequent urination, dizziness, or blood in your vomit) then go to the nearest Emergency Department.

Is it important to stay hydrated while taking semaglutide or tirzepatide?

Constipation and vomiting are both potential side effects of semaglutide and tirzepatide, and so it is important to stay hydrated while taking these medications. Drinking between 8 to 10 glasses a day of water can help prevent constipation. Vomiting causes loss of fluid, so it is especially important to stay hydrated if you develop this. Alcohol, caffeine, and sugary drinks are diuretics and will dehydrate you further, so you may need to drink even more water if you use these.

Are there kidney problems with semaglutide and tirzepatide?

Acute kidney injury (AKI) has been reported with semaglutide and other GLP-1 receptor agonists. While the exact mechanism is unknown, these cases may have occurred due to dehydration from gastrointestinal symptoms such as vomiting. Reassuringly, an analysis from multiple clinical trials found no difference in the number of people who developed AKI on semaglutide versus the number of people who developed AKI not on semaglutide. If you already have kidney disease and/or are on other medication(s) that affect your kidneys, please discuss this with your Aayu Well Medical doctor.

Eat Smaller, Frequent Meals

In addition to the side effects discussed above, GLP-1 receptor agonists like semaglutide and tirzepatide may have serious side effects. First, an increased number of diabetic retinopathy complications has been noted in clinical trials studying these medications. This effect was found later to occur mainly in patients who already had diabetic retinopathy before starting the drug, and it was largely related to how fast and by how much diabetes control improved during the first 4 months. Oral semaglutide (Rybelsus) has not been associated with an increased incidence of diabetic retinopathy and so may be used safely in these patients.

Another potentially serious side effect to consider with semaglutide and tirzepatide is medullary thyroid cancer (MTC). In the early stages of drug development, rodents receiving GLP-1 receptor agonist therapy developed a special type of thyroid tumor. However, it is not yet established whether this side effect extends to humans too. Importantly, humans have far fewer of the cells that lead to this tumor, and furthermore, our thyroid cells are likely much less responsive to GLP-1 receptor agonists. Nevertheless, GLP-1 receptor agonists, including semaglutide and tirzepatide, carry a black-box warning against their use in anyone with multiple endocrine neoplasia syndrome type 2, or a personal or family history of MTC.

Cases of pancreatitis have also been reported with use of GLP-1 receptor agonists, however acute cases were observed at similar rates between those who were and were not taking the drug in the SUSTAIN-6 clinical trial. GLP-1 receptor agonists do stimulate receptors in the pancreas which may lead to inflammation over time, but firm causality has not been established. They can be used safely in patients with a history of gallstone pancreatitis after gallbladder removal, but please discuss this with your doctor at Aayu Well if you have a history of pancreatitis.

Lastly, the FDA recently evaluated reports of suicidal thoughts or actions in patients treated with GLP-1 receptor agonists. A preliminary evaluation did not find any evidence that these medications cause these side effects, but investigation is ongoing. If you develop worsening depression, suicidal thoughts, or unusual changes in mood or behavior, then report them right away to your Aayu Well doctor. More information can be found at: https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type.