GLP-1 Safety: Semaglutide and Tirzepatide Risks, Side Effects and Warnings

Are semaglutide and tirzepatide safe?

Semaglutide and tirzepatide are prescription medicines with known risks. The FDA labels for the approved versions list a boxed warning about thyroid C-cell tumors seen in rodents, several serious warnings and common stomach-related side effects. Compounded versions are not FDA approved. A licensed provider reviews your health history before deciding whether either is appropriate.

This page summarizes safety information from the current FDA prescribing information for Wegovy and Ozempic (semaglutide) and Zepbound and Mounjaro (tirzepatide) [1][2][3][4], and from FDA information on compounded GLP-1 medicines [5][6]. It is general information, not medical advice.

Who should not take semaglutide or tirzepatide?

The FDA labels say not to use these medicines if you or a family member has had medullary thyroid carcinoma (MTC), if you have multiple endocrine neoplasia syndrome type 2 (MEN 2), or if you have had a serious allergic reaction to the medicine or its ingredients.

• Thyroid cancer history. In rodents, both medicines caused thyroid C-cell tumors. It is unknown whether they cause these tumors, including MTC, in humans [1][3].
• Serious allergy. Anaphylaxis and angioedema have been reported [1][3].
• Pregnancy. The Wegovy label says weight loss offers no benefit during pregnancy and may cause fetal harm. The Wegovy and Zepbound labels say to stop the medicine when a pregnancy is recognized [1][3]. Tell your provider if you are pregnant, planning a pregnancy or breastfeeding.
• Other conditions to disclose. Tell your provider about any history of pancreatitis, gallbladder disease, kidney disease, diabetic retinopathy or severe stomach problems such as gastroparesis, and about every medicine you take [1][3].

What are the common side effects?

The most common side effects in the FDA labels are gastrointestinal: nausea, diarrhea, vomiting, constipation and abdominal pain. Tell your provider about any side effect that bothers you or does not go away.

Other common reactions on the Zepbound label include indigestion, injection site reactions, fatigue, allergic reactions, burping, hair loss and acid reflux [3]. The Wegovy label also lists headache, dizziness, bloating and gas, among others [1]. Because compounded versions are not FDA approved, information about how often side effects occur with them is limited [5].

What are the serious warnings?

The FDA labels list several serious risks. Each is uncommon, but it is important to know the signs.

• Thyroid C-cell tumors (boxed warning). Watch for a lump or swelling in the neck, trouble swallowing, shortness of breath or hoarseness that does not go away [1][2][3][4].
• Pancreatitis. Severe stomach pain that does not go away, sometimes spreading to the back, with or without vomiting [1][3].
• Severe stomach side effects. All four labels warn that gastrointestinal reactions can sometimes be severe [1][2][3][4].
• Gallbladder disease. Gallstones and gallbladder inflammation have been reported. Signs can include pain in the upper stomach, fever, yellowing of the skin or eyes, or clay-colored stools [1][3].
• Low blood sugar. The risk is higher if you also take insulin or a sulfonylurea. Signs include shakiness, sweating, dizziness, confusion and a fast heartbeat [1][3].
• Kidney problems. Acute kidney injury has been reported, mostly in people who became dehydrated from nausea, vomiting or diarrhea. Drink fluids and tell your provider if you cannot keep fluids down [1][3].
• Serious allergic reactions. Swelling of the face, lips, tongue or throat, trouble breathing, a severe rash or a fast heartbeat [1][3].
• Diabetic eye problems. People with type 2 diabetes and a history of diabetic retinopathy should be monitored for changes in vision [1][3].
• Heart rate. The Wegovy label lists heart rate increase as a warning. Tell your provider if you feel your heart racing or pounding at rest [1].
• Anesthesia and procedures. These medicines slow stomach emptying. All four labels report rare cases of food or liquid entering the lungs during general anesthesia or deep sedation. Tell every provider about your medicine before any surgery or procedure [1][2][3][4].
• Birth control pills (tirzepatide). The Zepbound label advises switching to a non-oral method, or adding a barrier method, for 4 weeks after starting and for 4 weeks after each dose increase [3].

What about oral semaglutide, oral tirzepatide and microdosing?

FDA has approved semaglutide tablets: Rybelsus and Ozempic tablets for type 2 diabetes, and Wegovy tablets. Compounded oral tirzepatide and "microdosing" regimens have not been reviewed by FDA. The same safety warnings for the active ingredient still apply, and a licensed provider decides any dosing.

• FDA approved tablets. The Wegovy label says to take the tablet once daily on an empty stomach in the morning with up to 4 ounces of water, swallow it whole, and wait at least 30 minutes before eating, drinking or taking other oral medicines [1]. The semaglutide tablet labels carry the same boxed warning as the injections [1][7].
• Compounded oral tirzepatide. There is no FDA approved oral tirzepatide. Compounded versions are not FDA approved, and FDA does not review them for safety, effectiveness or quality [6].
• Microdosing. Lower or less frequent dosing than the label describes has not been reviewed by FDA. The same warnings and side effects listed above still apply. Follow only the dose your provider prescribes.

When should you contact your provider, and when should you seek emergency care?

Contact your provider for side effects that bother you or do not go away. Call 911 or go to the nearest emergency room for signs of a severe allergic reaction, severe ongoing stomach pain, trouble breathing, fainting, or thoughts of harming yourself.

Contact your provider if you have:

• Nausea, vomiting, diarrhea or constipation that does not improve
• Trouble keeping fluids down, or less urination than usual
• Mild signs of low blood sugar
• Changes in vision
• A new lump in your neck or hoarseness that does not go away
• A planned surgery or procedure, a new medicine, or a pregnancy

Seek emergency care right away. Call 911 for:

• Swelling of the face, lips, tongue or throat, or trouble breathing or swallowing
• Severe stomach pain that does not go away, with or without vomiting
• Severe low blood sugar, confusion, seizures or fainting
• Thoughts of suicide or self-harm. Call, text or chat the 988 Suicide & Crisis Lifeline at 988, or call 911 [8]

Telehealth messaging is not for emergencies.

What should you know about compounded versions?

Compounded semaglutide and compounded tirzepatide are not FDA approved. FDA does not review compounded drugs for safety, effectiveness or quality before they are marketed. They are not generic versions of Wegovy, Ozempic, Zepbound or Mounjaro and are not equivalent to them.

FDA has received reports of adverse events, some requiring hospitalization, that may be related to dosing errors with compounded injectable semaglutide. Some involved patients measuring the wrong dose and some involved dose miscalculations by health care professionals [5]. Compounded products may come in different concentrations or vials than the approved pens, so units and milliliters can differ from what you expect.

• Use only the syringe and instructions your pharmacy provides.
• Check the dose in units and milliliters on your label before each injection.
• Ask your provider or pharmacy if anything about your dose is unclear.
• Get compounded medicines only from a state-licensed pharmacy with a valid prescription.

At Stackhaus Health, prescribed compounded medicines are prepared by a state-licensed pharmacy for an individual patient, and the pharmacy's name appears on your label. See our official information page.

How does it work at Stackhaus Health?

You complete a free online intake about your health history and goals. A licensed provider reviews it and prescribes only if treatment is appropriate for you. Completing the intake does not guarantee a prescription. If prescribed, a state-licensed pharmacy prepares and ships it, and its name appears on your label.

Questions about your treatment? Contact support@stackhaushealth.com. See compounded semaglutide, compounded tirzepatide and tirzepatide vs semaglutide.