Key takeaways:
Retatrutide is a glucagon-like peptide-1 (GLP-1) medication that’s in clinical trials. Researchers are still determining retatrutide’s side effects.
In clinical trials, people receiving retatrutide reported mild side effects. These include nausea and vomiting, constipation, and a smaller appetite. Some people also experienced unusual sensations on their skin.
Retatrutide may have side effects common among other GLP-1 medications. Common GLP-1 side effects include heartburn, stomach pain, and diarrhea. Rare but serious side effects include low blood sugar, gallbladder problems, and pancreatitis.
Glucagon-like peptide-1 (GLP-1) drugs are a popular group of medications prescribed for weight loss, Type 2 diabetes, and more. And the number of medications in this class keeps expanding.
Retatrutide is an experimental GLP-1 drug that’s in clinical trials. It works slightly differently from existing medications, such as tirzepatide (Mounjaro, Zepbound). But its side effect profile seems to be similar.
So what are the known retatrutide side effects?
Retatrutide side effects at a glance
Researchers are still learning about retatrutide’s possible side effects. It’s typical not to have a side effects list until a medication is FDA approved.
In clinical trials, participants have reported the following side effects while receiving retatrutide:
Nausea
Vomiting
Constipation
Smaller appetite
Dysesthesia (an unusual sensation on your skin)
Because retatrutide works similarly to other GLP-1 medications, it may have similar side effects. Other common or mild GLP-1 side effects include:
Heartburn and indigestion
Bloating
Stomach pain
Injection-site reactions
Headache
Dizziness
Fatigue
Hair loss
Rarely, people using other GLP-1 medications have also reported more serious side effects, such as:
Hypoglycemia (low blood sugar)
Gallbladder problems, including gallstones
Pancreatitis (inflammation of the pancreas)
Kidney damage
Severe gastrointestinal (GI) complications, such as gastroparesis (slowed stomach emptying)
All approved GLP-1 medications also have a boxed warning for thyroid C-cell tumors. A boxed warning is the FDA’s strictest medication warning.
Below are four side effects reported by people receiving retatrutide in clinical trials.
1. Nausea and vomiting
Nausea and vomiting are some of the most commonly reported retatrutide side effects. They happen because retatrutide slows the movement of food through your gut and increases feelings of fullness. With GLP-1s, nausea and vomiting are usually most noticeable when you first start the medication. They typically improve over time.
These tips can help you manage nausea and vomiting at home:
Eat smaller meals throughout the day.
Remain upright for at least 30 minutes after eating.
Drink plenty of water.
Eat bland, easily digestible foods for a few days when nausea is at its worst.
Avoid foods that can trigger nausea, such as fatty, spicy, or greasy foods.
Limit or avoid alcohol and carbonated drinks.
Try drinking ginger or peppermint tea.
Ask a healthcare professional if you can safely take over-the-counter (OTC) nausea medications.
Severe vomiting can raise your risk of dehydration and (in serious cases) kidney damage. Seek medical help for severe or persistent vomiting.
2. Constipation
People using retatrutide in clinical trials also commonly reported constipation. Similar to nausea and vomiting, constipation can happen because retatrutide slows digestion. This is another common GLP-1 side effect that typically gets better over time.
Consider these tips to help manage constipation at home:
Slowly increase the amount of fiber in your diet.
Drink lots of water and other hydrating fluids.
Increase the amount of exercise you do. Try activities that are fun for you, such as dancing, walking, or yoga.
If these tips don’t work, speak with a healthcare professional. They may have other suggestions for you. And they will know if OTC constipation medications would be safe for you.
If constipation is severe or you have other symptoms, such as rectal bleeding, seek medical help.
3. Smaller appetite
People receiving retatrutide in clinical trials also reported a smaller appetite. This is typical with all GLP-1 medications. And for many, this side effect can contribute to other health goals, such as weight loss. So you may find it beneficial overall.
But it can be tough to eat when you don’t feel hungry. To ensure you’re getting adequate nutrition, aim for smaller portions of nutrient-dense foods. Consider these tips to get you started:
Drink smoothies. Blend together fruits, veggies, and protein.
Eat soups. Make sure they include veggies, whole grains, and protein.
Pick higher-protein yogurts. Greek yogurt is a good choice. You can also add nutritious toppings, such as granola or berries.
Eat eggs. They are nutrient dense and can be prepared in dozens of ways.
Add oatmeal to your recipe roster. This whole grain is a good source of fiber. Plus, you can mix in nutrient-filled toppings, such as berries, nut butters, and chia seeds.
If you have no appetite at all, tell a healthcare professional. They can help you get enough nutrition to support your health goals.
4. Unusual skin sensations
People receiving retatrutide also reported dysesthesia. This sensation can be unusual, unpleasant, or painful. Examples include a burning, tingling, or stinging sensation on your skin. In clinical trials, this retatrutide side effect was mild and very rarely caused a person to stop using the medication.
People using other GLP-1 medications, such as tirzepatide and semaglutide (Ozempic, Rybelsus, Wegovy), have also reported dysesthesia. Researchers aren’t sure if the medications directly cause it or if dysesthesia is triggered by rapid weight loss.
Speak to a healthcare professional if this side effect happens. In some cases, they may suggest pain relievers or topical numbing creams. But if it’s severe or too bothersome, you may need to stop the GLP-1 medication you’re using.
Other GLP-1 side effects
Retatrutide’s full side effect list isn’t available because it’s still being studied. But it may have similar warnings as other approved GLP-1 medications.
Most mild or common GLP-1 side effects, such as heartburn and diarrhea, affect the digestive tract. They typically improve as your body adjusts to the medication. Many of the tips for managing nausea, vomiting, and constipation can also help with other digestive side effects. But it’s a good idea to discuss it with a healthcare professional first.
Serious GLP-1 side effects
Most people with GLP-1 side effects do not have serious problems. But rarely, people have reported severe side effects. Here’s what you should know about serious GLP-1 side effects:
Low blood glucose (sugar): It’s rare for GLP-1 medications to cause low blood sugar on their own. But if you take other diabetes medications, you may have a higher risk. Make sure you treat low blood sugar quickly if it happens to you.
Gallbladder problems: People using GLP-1s have experienced gallbladder issues, including gallstones. Your risk may be higher if you’re using GLP-1s at higher doses or for long periods of time. If you have a history of gallbladder problems, tell your healthcare team.
Pancreatitis: People using GLP-1s have reported pancreatitis. It’s unclear whether the medications directly cause the condition. But if you have a history of pancreatitis, a GLP-1 might not be the best choice for you.
Kidney damage: Severe digestive side effects, such as vomiting, can raise your risk of sudden kidney damage. So be sure to seek help if you’re experiencing severe or persistent vomiting.
Severe GI complications: GLP-1s have also been linked to severe GI problems, such as gastroparesis. But it’s unclear whether these medications directly cause the condition. If you have a history of gastroparesis, GLP-1s are not recommended to use.
Thyroid C-cell tumors: Studies show that animals exposed to GLP-1s developed these types of thyroid tumors. This risk hasn’t been confirmed in humans. But to be safe, you shouldn’t use GLP-1s if you have a personal or family history of medullary thyroid cancer. You should also avoid them if you have an inherited condition called multiple endocrine neoplasia syndrome type 2.
The bottom line
Retatrutide is a glucagon-like peptide-1 (GLP-1) medication that’s in clinical trials. Common retatrutide side effects reported by study participants include nausea and vomiting, constipation, and a smaller appetite. Some people have also reported unusual sensations on their skin.
Researchers are still determining retatrutide’s side effects. But other GLP-1 medications commonly cause side effects such as diarrhea, heartburn, and stomach pain. Rare but serious GLP-1 side effects include low blood sugar, gallbladder problems, and pancreatitis.
Retatrutide may have similar side effects to other GLP-1 medications. More information will become available as the medication proceeds through clinical trials.
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References
Ahern, S. (2025). Allodynia and dysesthesia associated with semaglutide and tirzepatide. Cureus.
Begum, F., et al. (2024). Semaglutide-associated kidney injury. Clinical Kidney Journal.
Burke, O. M., et al (2025). Dermatologic implications of glucagon-like peptide-1 receptor agonist medications. Skin Appendage Disorders.
Eli Lilly and Company. (2025). Lilly’s triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial.
Shumway, N. K., et al. (2016). Neurocutaneous disease: Neurocutaneous dysesthesias. Journal of the American Academy of Dermatology.
