Important Safety Information: GLP-1 weight-loss medications

This page summarizes the most important safety information in the FDA prescribing information (labels) for GLP-1 medications approved for weight management: semaglutide, tirzepatide, liraglutide and orforglipron. It does not include everything in those labels. If a licensed provider prescribes one of these medicines for you, read the Medication Guide that comes with it.

This information comes from the labels of FDA-approved products. Compounded medications have no label approved by FDA. Compounded medications are not FDA-approved, and FDA does not review them for safety, effectiveness, or quality before they are marketed.

Boxed warning: risk of thyroid C-cell tumors

All four labels carry a boxed warning about thyroid C-cell tumors. In rats and mice, semaglutide, tirzepatide and liraglutide caused thyroid C-cell tumors, and it is unknown whether they cause these tumors, including medullary thyroid carcinoma (MTC), in people. The orforglipron label explains that orforglipron is not active in rats or mice and did not cause tumors in them, but that the human relevance of these GLP-1 related tumors seen in rodents has not been determined, so the same warning applies.

Do not use these medicines if you or a family member has had MTC, or if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Tell your provider if you notice a lump or swelling in your neck, trouble swallowing, shortness of breath or hoarseness that does not go away.

Who should not use these medicines

The labels list two contraindications: a personal or family history of MTC or MEN 2, and a prior serious allergic reaction to the medicine or its ingredients. Serious allergic reactions, including anaphylaxis and swelling of the face, lips or throat (angioedema), have been reported.

Serious risks

These are the serious risks the labels describe. A licensed provider weighs them against your health history.

Inflammation of the pancreas (pancreatitis): stop the medicine and get care if you have severe stomach pain that does not go away, with or without vomiting.
Gallbladder problems, including gallstones and inflammation, have occurred in clinical trials.
Severe stomach and bowel side effects can occur. The labels do not recommend these medicines for people with severe gastroparesis.
Kidney injury can follow dehydration from nausea, vomiting or diarrhea. The labels call for monitoring kidney function in people with these side effects.
Low blood sugar: the risk is higher when these medicines are used with insulin or certain diabetes pills (insulin secretagogues), whose dose may need to be lowered.
Diabetic eye disease (retinopathy) complications in people with type 2 diabetes: people with a history of diabetic retinopathy are monitored.
Heart rate increase is listed on the semaglutide and liraglutide labels.
Breathing in stomach contents (pulmonary aspiration) has been reported during general anesthesia or deep sedation. Tell every clinician who plans a surgery or procedure for you that you take one of these medicines.
A pen must never be shared between people, even if the needle is changed.

Pregnancy and birth control

The labels state that these medicines may cause harm to an unborn baby and should be stopped when pregnancy is recognized. The semaglutide label advises stopping at least 2 months before a planned pregnancy. Tell your provider if you are pregnant, plan to become pregnant or are breastfeeding.

Tirzepatide and orforglipron can make birth control pills less reliable. The tirzepatide 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; the orforglipron label gives 30 days for each. Methods that are not taken by mouth should not be affected.

Common side effects

The most common side effects in the labels are stomach and bowel effects: nausea, diarrhea, vomiting, constipation, abdominal pain, indigestion, belching and reflux. The labels also list fatigue, headache, dizziness and hair loss, and injection site reactions for injected products. Tell your provider about side effects that bother you or do not go away.

Tell your provider about other medicines

These medicines slow how fast the stomach empties, which can change how other medicines taken by mouth are absorbed. Tell your provider about every medicine you take, especially insulin, diabetes medicines and blood thinners such as warfarin.

When to get medical help right away

Call 911 or get emergency care for signs of a severe allergic reaction, such as swelling of the face, lips, tongue or throat, trouble breathing or fainting. Contact your provider promptly for severe or lasting stomach pain, pain in the upper right belly, yellowing of the skin or eyes, signs of dehydration, vision changes, or a lump in your neck.

You can report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Who decides

A licensed provider reviews your history and labs and decides whether one of these medicines is appropriate for you.

Prescription treatment requires an evaluation by a licensed healthcare provider, who decides whether treatment is appropriate for you. Not everyone qualifies. Completing an assessment, booking a visit, or paying a fee does not guarantee a prescription.