GLP-1 Contraindications

GLP-1 receptor agonists are well-tolerated by most patients but have specific contraindications and cautions that matter. This page is a clinical reference.

Absolute contraindications

Personal or family history of medullary thyroid carcinoma (MTC)

The class carries a boxed warning regarding MTC based on rodent studies. Patients with personal history of MTC or first-degree family history are contraindicated. Human evidence of MTC causation is limited, but the warning is regulatory standard across the class.

Multiple Endocrine Neoplasia syndrome type 2 (MEN-2)

MEN-2 predisposes to medullary thyroid carcinoma. Contraindication is the same as MTC history.

Pregnancy

Animal data suggest fetal harm. Stop semaglutide ≥2 months and tirzepatide ≥1 month before any planned conception. If conception occurs during therapy: stop immediately and notify OB.

Known serious hypersensitivity to the drug

Anaphylaxis or angioedema with prior GLP-1 agonist therapy.

Strong cautions

History of pancreatitis

The class label warns of pancreatitis risk. Patients with prior pancreatitis can be considered case-by-case, with informed consent. Acute pancreatitis during therapy = stop immediately, evaluate.

Severe gastrointestinal disease

Pre-existing gastroparesis is a relative contraindication — the gastric-emptying delay can worsen symptoms. Active inflammatory bowel disease flare warrants caution.

Severe hepatic impairment

Limited safety data in Child-Pugh C cirrhosis. Use only if benefit clearly outweighs risk and with hepatology coordination.

Severe renal impairment

Most agents have specific dosing or use guidance at eGFR <30. FLOW data established that semaglutide is beneficial in CKD including stage 4; however, dehydration from GI side effects can precipitate AKI. Monitor closely.

Active eating disorder

Active anorexia nervosa, bulimia, or severe binge eating disorder requires specialized eating-disorder care; GLP-1 therapy is generally not appropriate during active eating disorder symptoms.

Conditions requiring extra monitoring

• Diabetic retinopathy — rapid A1c reduction can transiently worsen diabetic retinopathy. Ophthalmology coordination if proliferative disease.
• Severe heart failure with low ejection fraction — limited trial data; emerging guidance from STEP-HFpEF applies primarily to HFpEF.
• Severe depression with prior suicidality — investigated as a class signal; current FDA position is that causation is not established. Monitor; do not withhold therapy reflexively.
• Cholelithiasis history — rapid weight loss raises gallstone risk; monitor for biliary symptoms.

Drug-drug considerations

See our comprehensive drug interactions reference. Highest-stakes: insulin and sulfonylureas (hypoglycemia), anesthesia/surgery (aspiration risk — hold ≥1 week), oral contraceptives (tirzepatide specifically — backup contraception recommended).

Age considerations

• Children <12: Not approved.
• Adolescents 12+: Wegovy and Saxenda approved.
• Elderly: No specific upper age limit. Watch for dehydration and AKI; monitor for sarcopenia.

How telehealth providers handle contraindications

Most reputable providers screen for contraindications via intake questionnaire and require clinician confirmation. Patients does not omit relevant history — this is the kind of thing that matters.