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Medication-associated angioedema — ABIM Board MCQ

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HardDipeptidyl Peptidase-4 InhibitorsMedication-associated angioedemaABIM Board

A 68-year-old Black man with type 2 diabetes mellitus and hypertension presents with rapidly progressive swelling of the tongue and floor of the mouth. He has no urticaria, pruritus, wheezing, or hypotension. He has taken lisinopril and amlodipine for 8 years and metformin for 5 years. Sitagliptin was added 12 days ago. There are no new foods or other medications. Despite intramuscular epinephrine, an H1 antihistamine, and glucocorticoids, the swelling progresses, and he undergoes awake fiberoptic intubation. Serum C4 and C1 esterase inhibitor levels are normal. His renal function is normal. After airway stabilization, which of the following is the most appropriate long-term medication strategy?

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Correct answer: D — Discontinue lisinopril and sitagliptin

This patient has life-threatening medication-associated angioedema. Tongue and floor-of-mouth swelling without urticaria, pruritus, bronchospasm, or hypotension—and progression despite standard anaphylaxis therapy—supports a bradykinin/substance P-mediated process. ACE inhibitor angioedema can begin after many uneventful years of treatment, so the long duration of lisinopril use does not exonerate it. Continuing an ACE inhibitor after angioedema substantially increases recurrence risk; lisinopril must therefore be discontinued and avoided. Sitagliptin was started within the characteristic early window for reported sitagliptin-associated angioedema. DPP-4 participates in substance P degradation, and DPP-4 inhibition can increase susceptibility to ACE inhibitor-associated angioedema. FDA labeling directs discontinuation of sitagliptin when a serious hypersensitivity reaction such as angioedema is suspected. Because both drugs plausibly contributed to a severe airway event, both should be stopped. A is tempting because lisinopril is the classic cause, but it ignores the newly introduced potentiating drug. C incorrectly retains the ACE inhibitor despite a class adverse effect that can occur after years. D appropriately removes lisinopril but unnecessarily stops metformin, which does not cause this syndrome and is safe with normal renal function. E removes sitagliptin but retains lisinopril and incorrectly implicates amlodipine.

Reference: BRYNOVIN (sitagliptin) Prescribing Information (2025) — https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219122s000lbl.pdf Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitor-associated angioedema (2009) — https://pubmed.ncbi.nlm.nih.gov/19581505/ Recurrent angiotensin-converting enzyme inhibitor-associated angioedema (1997) — https://pubmed.ncbi.nlm.nih.gov/9218671/