Who Shouldn't Take GLP-1 Drugs: Contraindications, Cautions, and Honest Patient Profiles

There is a short list of patients who should not take a GLP-1 receptor agonist. It is not the long list you might be picturing. The FDA labels for Wegovy and Zepbound name two absolute contraindications each, several warnings, and a handful of patient profiles where the risk-benefit case is uncertain. The boundary between those three buckets is where most telehealth intakes get sloppy.

Asynchronous intake forms do not always surface the family-history questions the prescribing information says have to be asked. If you are about to fill in a Hims, Ro, NovoCare, or LillyDirect intake, the checklist below is what we would want a friend to have in front of them.

Absolute Contraindications, From the FDA Labels

Both labels list an identical pair. There are no other absolute contraindications.

Personal or family history of medullary thyroid carcinoma (MTC) or MEN2 syndrome. Section 4 of both the Wegovy label and the Zepbound label. The basis is rodent data: in two-year studies, both molecules caused dose-dependent thyroid C-cell tumours in rats. Human relevance is unknown. The family-history piece matters because MEN2 is autosomal dominant; a first-degree relative with MTC is a question the prescribing information asks the clinician to ask.

Previous serious hypersensitivity to the molecule. Both labels list anaphylaxis and angioedema in post-marketing surveillance.

Pregnancy. Both labels contraindicate the drug in pregnancy and instruct discontinuation at least 2 months before planned conception because of the long half-life. Animal studies showed fetal harm; human data is too sparse to characterise risk. Both manufacturers maintain pregnancy registries.

Strong Cautions, From the Warnings Section

Pancreatitis history. Acute pancreatitis is in Warnings on both labels. Patients with pancreatitis history were excluded from the pivotal SUSTAIN, STEP, and SURMOUNT trials, so there is no dataset in that population. Most obesity-medicine specialists treat a prior episode as a strong reason to choose a different agent.

Gallbladder disease. Cholelithiasis: 1.6% on Wegovy vs 0.7% placebo; 1.1% vs 1.0% on Zepbound. Cholecystitis: 0.6% vs 0.2% on Wegovy; 0.7% vs 0.2% on Zepbound. Substantial weight loss from any cause raises gallstone risk, so the attribution is mixed.

Severe gastroparesis. The drugs work in part by slowing gastric emptying; severe pre-existing gastroparesis can tip from "slowed" into "non-functional". The AGA rapid practice update advises against use in that group. Mild gastroparesis is the grey zone.

Diabetic retinopathy progression in T2D. In SUSTAIN 6, retinopathy complications were observed at a higher rate in the semaglutide arm than placebo, suspected to be rapid glycaemic improvement rather than the drug itself. The label recommends monitoring patients with a retinopathy history.

Acute kidney injury during dehydration. Severe nausea and vomiting can produce dehydration; dehydration with any baseline kidney impairment is the documented mechanism for the AKI cases in post-marketing surveillance. The kidney itself is not a contraindication; the kidney plus a vomiting episode is.

Patient Profiles Where the Case Is Uncertain

Adolescents. Wegovy was approved for ages 12+ on December 23, 2022 based on STEP TEENS (FDA approval letter). Zepbound is not yet approved for under-18 weight management; the SURMOUNT-ADOLESCENTS trial is ongoing. Long-term safety data in 12-to-17-year-olds is much thinner than in adults; the decision belongs with a paediatric obesity specialist, not an adult telehealth intake.

Older adults at risk of sarcopenia. A 2025 review put the proportion of GLP-1 weight loss attributable to lean mass at 25-40%. For a 70-year-old at BMI 35, losing 20% of body weight with 30% from lean mass is a different calculation than for a 45-year-old. Pre-existing sarcopenia, frailty, or a falls history sharpens the case for slower titration, a lower target, or a different approach.

Active eating-disorder history. For active restrictive disorders (anorexia, ARFID), GLP-1s are widely considered contraindicated by eating-disorder specialists (NEDA position); appetite suppression compounds the restriction. For binge-eating disorder the picture is less settled — they may reduce binge frequency but do not address the underlying mechanism. Any history, including remitted disease, is information the prescriber needs.

Drug Interactions Worth Knowing

Oral medications and gastric emptying. The Zepbound label reports that a single 5 mg dose reduced peak ethinyl estradiol concentration by 59% and norgestimate by 66% when co-administered with a combined oral contraceptive. The label recommends switching to a non-oral method, or adding a barrier, for four weeks after starting Zepbound and after each dose escalation. Wegovy carries a more general delayed-gastric-emptying warning. Patients on narrow-therapeutic-index drugs (warfarin, thyroid hormone, certain seizure medications) should discuss timing with their prescriber.

Insulin and sulfonylureas in T2D. Combined with insulin or a sulfonylurea, hypoglycaemia risk rises. The label instruction is to consider reducing the concomitant agent at GLP-1 initiation.

Perioperative anaesthesia. The October 2024 multi-society guidance replaced the stricter June 2023 ASA advice. Most patients can continue their GLP-1 through elective surgery, with extra precautions for higher doses or dose escalation: a 24-hour clear-liquid diet, gastric ultrasound where available, and consideration of rapid-sequence induction. Tell your anaesthesiologist at least a week before any procedure.

What Gets Missed in Telehealth Intakes

Intake forms usually ask "do you have thyroid disease?" rather than "has any first-degree relative had medullary thyroid carcinoma?" The two questions are not the same. Gallbladder and pancreatitis history are commonly buried in a free-text "any other conditions?" box. Self-advocacy is surfacing these proactively.

What to Bring to Your Prescriber

• Personal thyroid history: surgery, nodules, biopsy, or known cancer.
• Family thyroid history: any first-degree relative with MTC or MEN2.
• Pancreatitis history: any prior episode, plus upstream risks (heavy alcohol, high triglycerides, gallstones).
• Gallbladder history: whether you still have one, prior stones, prior cholecystitis.
• Current medications: oral contraceptives, warfarin or other narrow-therapeutic-index drugs, insulin or sulfonylureas, diuretics.
• Eating-disorder history: including remitted disease.
• Pregnancy plans: pregnant, possibly pregnant, planning to conceive within 12 months, breastfeeding.
• Surgical plans: any elective procedure under sedation in the next 6 months.
• Kidney function: most recent eGFR if known.
• Retinal screening (T2D only): date of most recent dilated eye exam.

If your prescriber works through this list, the conversation is working. If not, you have a sourced list to walk them through.

The Honest Grey Zone

Mild functional dyspepsia, mild GORD, and well-controlled IBD are not contraindications, but GI side effects can mask or mimic a flare; a slower titration is reasonable. eGFR 45-60 is not a contraindication but lowers the AKI margin if dehydration occurs. A history of depression or anxiety is not a contraindication; the FDA has investigated post-marketing suicidality signals and not so far attributed them to the drug class. These decisions belong with a clinician who has your full history.

What This Article Is Not

Not a list of reasons not to take a GLP-1. The benefit case for many patients is substantial; STEP-1 showed 14.9% mean weight loss at 68 weeks for semaglutide, SURMOUNT-1 showed 22.5% for tirzepatide. For a patient with no contraindication and no relative caution, the case is one of the strongest in modern pharmacotherapy. The point of this article is the specific contexts where the drug is wrong, or where the case deserves a real clinical conversation rather than a 15-minute intake.

How we keep this article current

We refresh this page on any FDA label change or new society position that touches contraindications, warnings, or perioperative guidance. A few areas tend to drift faster than the rest:

• Pediatric guidance. Zepbound's adolescent indication is in trial; Wegovy's 12+ indication has been live under four years, so the evidence base is still maturing.
• Perioperative guidance. It changed in October 2024 and is likely to revise again as gastric-ultrasound evidence accumulates.
• Pregnancy data. It is being collected prospectively through manufacturer registries; the 2-month-before-conception window is a pharmacokinetic calculation that may move once outcome data is in.

If you spot a label change or a new society position we have missed, email [email protected].

For the mechanism behind the contraindications, see how GLP-1 drugs work. For the head-to-head, see Wegovy vs Zepbound. Our editorial process is on the methodology page; the disclaimer applies.

Methodology: this article describes the FDA-labelled contraindications and warnings for semaglutide (Wegovy) and tirzepatide (Zepbound), supplemented by society guidance from the ASA, AGA, and NEDA, and peer-reviewed reviews of GLP-1 use in older adults. It does not constitute medical advice. The article is awaiting review by our named medical reviewer; clinical recommendations should not be acted on until the page is re-tagged as reviewed.