Some people should not take a GLP-1 medication at all. The absolute contraindications on the current FDA labels for semaglutide and tirzepatide are short and specific: a personal or family history of medullary thyroid carcinoma, the inherited syndrome multiple endocrine neoplasia type 2 (MEN 2), and a known serious allergic reaction to the drug or its ingredients. Pregnancy is a stop as well. Everything else below is a caution rather than a disqualification, meaning it changes how you are screened, dosed and monitored, not whether you can be treated at all.
The absolute contraindications
Both the Wegovy (semaglutide) prescribing information and the Zepbound (tirzepatide) prescribing information carry a boxed warning about thyroid C-cell tumors. In rodents, these drugs cause C-cell tumors at clinically relevant exposures. The labels are explicit that it is unknown whether the same thing happens in humans, because the human relevance of the rodent finding has not been determined.
That is worth saying plainly. This is a precautionary contraindication built on animal data, not a proven human cancer risk. It is also non-negotiable. If you or a first-degree relative has had medullary thyroid carcinoma, or if MEN 2 runs in your family, these medications are off the table and no prescriber should work around it.
The second contraindication is a known serious hypersensitivity to the medication or its excipients. Anaphylaxis and angioedema have been reported after marketing.
Pregnancy, breastfeeding and planning a family
If you are pregnant, these drugs are stopped. The tirzepatide label states the drug may cause fetal harm and should be discontinued when pregnancy is recognized. Weight loss during pregnancy is not the goal, and the safety data in humans is not there.
If you are planning to conceive, timing matters more than most people expect. Because semaglutide has a long half-life, the label advises discontinuing at least two months before a planned pregnancy. That is a real planning window, not a formality.
Two details that get missed:
- Tirzepatide can reduce the effectiveness of oral contraceptives. The label advises switching to a non-oral method, or adding a barrier method, for four weeks after starting and for four weeks after each dose increase. People have conceived unintentionally on this exact gap.
- For breastfeeding, the oral semaglutide tablet carries specific caution because of an absorption enhancer that appears in human milk, and the label points toward alternative formulations. Nursing should be an individual conversation, not an assumption in either direction.
Conditions that mean caution, not automatic exclusion
Severe gastroparesis. Both labels state the drug is not recommended in severe gastroparesis. These medications slow gastric emptying by design, so adding them to stomach that already empties poorly is the wrong direction.
A history of pancreatitis. Acute pancreatitis, including fatal cases, has been observed with GLP-1 receptor agonists. A previous episode is not listed as a formal contraindication, but it is a genuine reason for a careful conversation rather than a box to tick past.
Gallbladder disease. Gallstones and cholecystitis occur more often on these drugs, partly because rapid weight loss itself raises gallstone risk. Active gallbladder disease needs to be addressed first.
Type 1 diabetes and insulin use. The semaglutide label states use in type 1 diabetes, or in combination with insulin, has not been evaluated for weight management. Anyone on insulin or a sulfonylurea needs those doses reviewed before starting, because the hypoglycemia risk is real.
A history of diabetic retinopathy. Retinopathy complications have been reported in semaglutide trials, and the labels advise monitoring people with existing retinopathy.
Significant depression or past suicidal ideation. Both labels advise monitoring for depression and suicidal thoughts and discontinuing if they develop. This is not a reason to be refused care, but it is a reason for someone to actually be watching.
Kidney concerns. There are postmarketing reports of acute kidney injury, mostly in people who became volume depleted from vomiting or diarrhea. Dehydration is the mechanism, which makes it largely preventable.
Two things that change the plan rather than blocking it
If you have surgery or an endoscopy scheduled, tell the team you are on a GLP-1. The multisociety guidance published in 2024 moved away from routinely stopping these drugs before elective procedures and now suggests most patients can continue, with a liquid diet for 24 hours beforehand for those at highest risk of gastrointestinal effects. Follow your surgical team, not a blog.
Because these drugs delay gastric emptying, they can also affect absorption of other oral medications. Bring your full list, including thyroid medication and anything with a narrow margin.
Red flags that mean call, not wait
- Persistent severe abdominal pain, especially if it radiates to the back, with or without vomiting
- Vomiting or diarrhea you cannot keep ahead of, or signs of dehydration such as very little urine
- A lump in the neck, hoarseness that does not resolve, or trouble swallowing
- Swelling of the face, lips or throat, or trouble breathing
- New or worsening thoughts of self-harm
- Sudden vision changes if you have diabetes
Where you get it matters too
The FDA has warned about unapproved and illegally sold GLP-1 products, including salt forms of semaglutide whose properties are not established, and has received reports of patients harmed by measuring and self-administering the wrong dose. Products sold as research chemicals or priced far below anything legitimate are not a shortcut. If you want the honest comparison, read our piece on compounded semaglutide versus the brand name.
What proper screening looks like
A responsible GLP-1 consult covers personal and family thyroid history, pregnancy plans and contraception, gallbladder and pancreatic history, current medications including insulin, kidney function, mental health history and any upcoming procedures. If nobody asked you these questions, you were sold a product, not treated.
Our medical weight loss program is built around that screening and the follow-up that comes after it. If you are already on treatment and dealing with symptoms, our guide to GLP-1 side effects covers what is expected and what is not.
Medically reviewed by Krishna Borges, MSN, APRN, FNP-C. This article is for general education and is not a substitute for individual medical advice.