Source of Contraindications of incretin therapy

{{Infobox concept | name = Contraindications of incretin therapy | subtitle = Clinical practice | Absolute, labelled = Personal or family history of medullary thyroid carcinoma; MEN 2 | Also labelled = Prior hypersensitivity to the product | Cautions = Pancreatitis history, severe gastroparesis, pregnancy }} '''Contraindications of incretin therapy''' are the circumstances in which product labelling directs that a [[GLP-1 receptor agonist|GLP-1 receptor agonist]] or [[Dual incretin agonist|dual agonist]] is not used. They differ in detail between products and jurisdictions, and this article describes the general pattern rather than any particular label.{{r|ada2024}} The labelled contraindications for the class are a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, and prior serious hypersensitivity to the product or an excipient. The first derives from rodent C-cell findings and is precautionary; see [[Adverse effects of GLP-1 receptor agonists]].{{r|drucker2018}} A larger set of cautions rather than contraindications covers pancreatitis history, severe pre-existing gastroparesis, pregnancy and breastfeeding, and combination with insulin or sulfonylureas. See [[Pregnancy and incretin therapy]] and [[Hypoglycaemia]].{{r|ada2024}} == Labelled contraindications == The thyroid contraindication is the distinctive one for this class. Rodent studies showed C-cell hyperplasia and tumours at high exposure; human C cells express the receptor at far lower density and no human signal has been established, but the contraindication is retained as a precaution.{{r|drucker2018}} Hypersensitivity contraindications are ordinary for any injected peptide and cover both the active substance and excipients. Reactions specific to a formulation component do not necessarily extend to another product containing the same peptide. Product labels also carry a substantial set of warnings that are not contraindications — pancreatitis, gallbladder disease, retinopathy in the context of rapid glycaemic improvement, and the perioperative considerations discussed at [[Aspiration risk under anaesthesia]].{{r|ada2024}} == Cautions and interactions == | Circumstance | Consideration | |---|---| | Concurrent insulin or sulfonylurea | Reduce the background agent; hypoglycaemia risk | | Severe gastroparesis | Delayed emptying may worsen symptoms | | Prior pancreatitis | Causality unestablished; caution conventional | | Pregnancy or planning | Not recommended; weight loss undesirable in pregnancy | | Severe renal impairment | Dehydration from vomiting can precipitate injury | Renal considerations are indirect for most of this class: the peptides are not renally cleared to a degree requiring dose adjustment, but persistent vomiting and reduced intake can precipitate acute kidney injury in someone with limited reserve.{{r|ada2024}} Interaction with oral medicines is a rate rather than an extent effect for most drugs, arising from delayed emptying. See Drug interaction with oral absorption.{{r|nauck2016}} Trial populations excluded several of the groups listed above, so the evidence in them is correspondingly thin.{{r|wilding2021}} == Scope of this article == Contraindications are properties of labelled products in defined jurisdictions. Compounds sold for research use have no labelling and no approved indication, so the concept does not apply to them in the regulatory sense at all.{{r|drucker2018}} That is not a reason to disregard the clinical information. It is a reason to be clear about its provenance: the contraindications described here come from the labelling of approved products and are not statements about unapproved material. Nothing on this wiki is medical advice, and research-use compounds are not approved for human administration. See [[Research use only]].{{r|ada2024}} == References == {{reflist}} <ref name="ada2024">American Diabetes Association. "Standards of Care in Diabetes." ''Diabetes Care'' 47(Suppl 1) (2024).</ref> <ref name="drucker2018">Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." ''Cell Metabolism'' 27(4):740–756 (2018). PMID 29617641.</ref> <ref name="nauck2016">Nauck MA, Meier JJ. "The incretin effect in healthy individuals and those with type 2 diabetes." ''The Lancet Diabetes & Endocrinology'' 4(6):525–536 (2016). PMID 26876794.</ref> <ref name="wilding2021">Wilding JPH, Batterham RL, Calanna S, et al. "Once-weekly semaglutide in adults with overweight or obesity." ''New England Journal of Medicine'' 384(11):989–1002 (2021). PMID 33567185.</ref> == See also == * [[Adverse effects of GLP-1 receptor agonists]] * [[Hypoglycaemia]] * [[Aspiration risk under anaesthesia]] * [[Pregnancy and incretin therapy]] * [[Prescribing information]] {{DEFAULTSORT:Contraindications of incretin therapy}} [[Category:Contraindications and cautions]] [[Category:Clinical practice]] [[Category:Adverse effects]]