Who Should Not Take a GLP-1

A large share of GLP-1 prescriptions now originate from an online intake form that takes about ten minutes and is reviewed asynchronously. Some of those services are careful. Some of them are a checkbox exercise.

This piece is the screening conversation I would have with you, in the order I would have it. If you have not been asked most of these questions by whoever is prescribing for you, that tells you something useful about the supervision you are receiving.

The absolute contraindications

There are two, and they are not judgement calls.

Medullary thyroid carcinoma and MEN2

Do not take these drugs if you have a personal or family history of medullary thyroid carcinoma, or of multiple endocrine neoplasia syndrome type 2.

The origin is rodent studies, in which GLP-1 receptor agonists caused thyroid C-cell tumours. Whether this translates to humans is genuinely unestablished — rodent C-cells differ from human C-cells in their receptor density, and the human data has not shown a clear signal. But the contraindication is firm, it is on every label in the class, and it is not something to negotiate around.

Note that this is family history, not only personal. If you do not know, it is worth asking.

Known serious hypersensitivity

Prior serious hypersensitivity reaction to the drug or its components. Rare, and self-evident.

Pregnancy, and the part people are not told

These drugs are not for use during pregnancy. Animal reproductive toxicity data showed adverse effects, human data is limited, and a substantial energy deficit is not what a pregnancy needs.

Three specifics that get missed:

Plan the washout. Semaglutide’s labelling recommends discontinuing at least 2 months before a planned pregnancy, because it clears slowly. Tirzepatide’s is shorter. If pregnancy is anywhere on your horizon, that timeline belongs in the conversation before you start.

Fertility can return without warning. These drugs improve insulin sensitivity and can restore ovulation in people who were not ovulating — particularly with PCOS, where I have written about this at more length. People who spent a decade being told conception would be difficult are conceiving quickly, on a medication that is contraindicated in pregnancy.

Tirzepatide interacts with oral contraceptives. Delayed gastric emptying reduces their absorption enough that it is in the label: use a non-oral method or add a barrier method for 4 weeks after starting and 4 weeks after each dose increase. If you take a pill and nobody told you this, that is worth a conversation this week.

Breastfeeding is also an exclusion; the drugs are not recommended during lactation.

The situations that need a real conversation

These are not “no.” They are “not without someone actually thinking about it.”

Prior pancreatitis. Pancreatitis is a rare but recognised risk in this class. A prior episode does not automatically exclude you, but it changes the risk calculation and it needs to be weighed by someone who knows the details of that episode.

Active gallbladder disease. Rapid weight loss from any cause raises gallstone risk, and there is a gallbladder signal in the GLP-1 data specifically. Active symptomatic disease should generally be addressed first.

Severe gastroparesis. Adding a drug whose mechanism includes slowing gastric emptying to a stomach that already empties poorly is a predictable problem.

Proliferative diabetic retinopathy. In SUSTAIN-6, an increased rate of retinopathy complications was seen in participants with pre-existing retinopathy and poor baseline glycaemic control, plausibly related to the speed of glucose improvement rather than the drug itself. Anyone with significant retinopathy should have an ophthalmology plan before and during treatment.

Significant kidney or liver disease. Not exclusions in themselves, but they change monitoring, and dehydration from GI side effects matters much more in this group.

On insulin or a sulfonylurea. Not an exclusion — but those doses will usually need reducing, because eating substantially less while taking a drug that lowers glucose is how people end up hypoglycaemic. This requires active management, not a warning.

Things that are wrongly treated as exclusions

I want to spend a moment here, because I keep meeting people who were refused care over these.

A history of depression. Not a contraindication. A safety signal linking this class to suicidal thoughts was raised from spontaneous adverse-event reports in 2023; both the FDA and the European Medicines Agency reviewed it and did not find evidence of a causal association. A psychiatric history is a reason to say so at the start, agree what you are both watching for, and continue existing treatment — not a reason to be turned away.

A history of an eating disorder. This one deserves care rather than a blanket rule. Appetite suppression can interact badly with restrictive patterns, and the culture around these drugs is saturated with the exact framing that is unhelpful. But excluding this group entirely denies effective treatment to people who frequently have the most to gain. The right answer is coordinated care with a mental health clinician, monitoring agreed in advance, and an emphasis on adequate intake rather than on the scale.

Being older. Age is not a contraindication. It changes the emphasis considerably — lean mass and bone become the central concern rather than a footnote, and I would be more insistent about protein, resistance training, and a baseline DXA. But that is a modified plan, not a refusal.

Having a BMI “not high enough” in someone’s opinion. Approval criteria are specific and comorbidities count. That is a coverage conversation, not a safety one.

The one nobody remembers: procedures

If you are having surgery, an endoscopy, a colonoscopy, or anything with sedation, your anaesthetist needs to know. Say it out loud in pre-op, unprompted, and do not assume it reached the chart.

Delayed gastric emptying means your stomach may not be empty after the standard fasting period, which raises aspiration risk. The guidance here has evolved — early advice was fairly blanket withholding, while 2024 multisociety guidance favours risk stratification, clear liquids the day before, and gastric ultrasound where available. Which version your institution follows does not change your instruction, which is simply to tell them.

Screening questions to ask yourself

Before your first appointment, have answers ready for:

1. Has anyone in my family had medullary thyroid cancer or MEN2?
2. Am I pregnant, could I be, or might I want to be within the next year?
3. Do I take an oral contraceptive?
4. Have I ever had pancreatitis or gallbladder disease?
5. Do I take insulin or a sulfonylurea?
6. Do I have retinopathy, and when was my last eye exam?
7. Do I have a psychiatric or eating disorder history my prescriber should know about?
8. Do I have any procedure scheduled in the next 3 months?

Two of the situations on this page have their own articles, because “requires a real conversation” is not much use without knowing what the conversation is about: gastroparesis, where the drug’s own mechanism is the problem, and the thyroid cancer warning. If you are under 18, the calculus is different again — GLP-1s for teenagers. And the cancer question people arrive with, which is broader than the thyroid one, is answered in GLP-1s and cancer risk.

On that last one: anaesthesia and a stomach that empties slowly is a specific combination, and the instruction is to tell them unprompted — GLP-1s, surgery and procedures. The thyroid item at the top of this list is the only absolute contraindication here, and where it comes from is worth understanding rather than just obeying — the thyroid cancer warning, explained.

If your prescriber does not ask you most of these, ask them why not. It is a reasonable question and a good clinician will not mind it.

Two timing figures belong in this conversation as well. These drugs persist for 4–5 weeks after the last dose, which is why pregnancy planning is discussed in months rather than days, and why an anaesthetist needs to know even if you skipped a dose. And any procedure in the next 3 months is worth raising now rather than at the pre-op appointment.