Well-tolerated by most but specific contraindications and cautions matter.
Absolute
Personal/family history of MTC
Class boxed warning based on rodent studies. Personal history or first-degree family history is contraindicated. Human evidence is limited but warning is regulatory standard.
MEN-2
Predisposes to MTC. Same contraindication.
Pregnancy
Animal data suggest fetal harm. Stop semaglutide ≥2 months and tirzepatide ≥1 month before planned conception. Pregnancy during therapy: stop immediately, notify OB.
Known serious hypersensitivity
Anaphylaxis or angioedema with prior GLP-1 RA therapy.
Strong cautions
History of pancreatitis
Class label warns of pancreatitis. Prior pancreatitis can be considered case-by-case with informed consent. Acute pancreatitis during therapy = stop, evaluate.
Severe GI disease
Pre-existing gastroparesis is relative contraindication. Active IBD flare warrants caution.
Severe hepatic impairment
Limited safety data in Child-Pugh C cirrhosis.
Severe renal impairment
Most agents have specific dosing at eGFR <30. FLOW established sema benefit in CKD including stage 4; but dehydration from GI side effects can precipitate AKI.
Active eating disorder
Active anorexia, bulimia, or severe binge eating disorder requires specialized care; GLP-1 generally not appropriate during active symptoms.
Extra monitoring
- Diabetic retinopathy — rapid A1c reduction can transiently worsen. Ophthalmology coordination if proliferative disease.
- Severe HF with low EF — limited trial data; STEP-HFpEF applies to HFpEF.
- Severe depression with prior suicidality — class signal investigated; FDA position: causation not established. Monitor; don't withhold reflexively.
- Cholelithiasis history — rapid weight loss raises gallstone risk; monitor for biliary symptoms.
Age
- Children <12: not approved
- Adolescents 12+: Wegovy and Saxenda approved
- Elderly: no upper age limit. Watch dehydration/AKI; monitor sarcopenia.