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Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: While the link between bradykinin induced angioedema and angiotensinconverting enzyme inhibitors (ACEI) is well established, less data exists on angioedema resulting from the concomitant use of ACEI with other medications. We describe a case of life-threatening angioedema precipitated by the dual action of an ACEI and a dipeptidyl peptidase-IV (DPP-IV) inhibitor. Methods: A 49 year-old male with a history of hypertension treated with an ACEI (lisinopril) for the past 3 years and type 2 diabetes treated with metformin presented to the emergency department with a sudden onset of oropharyngeal and laryngeal swelling, dysphagia, hoarse voice and difficulty breathing. The patient was taken emergently to the operating room where he underwent fiberoptic intubation, which revealed extensive airway edema. He was transferred to the intensive care unit (ICU) for continued care. During his ICU course, he was treated with epinephrine, methylprednisolone, and diphenhydramine. The angioedema resolved and the patient was extubated after 4 days of mechanical ventilation. Family history was negative for hereditary angioedema and the complement C4 assay was negative. A thorough review of the patient’s medications revealed the addition of a DPP-IV inhibitor (sitagliptin) 1 week prior to presentation. Both lisinopril and sitagliptin were discontinued for concern of medication induced angioedema. Upon discharge, education was provided on avoiding the use of lisinopril and sitagliptin. Results: Angioedema is a well-recognized side effect of ACEI, however the potential for this complication is greatest during the first weeks after treatment initiation. DPP-IV inhibitors are a relatively new class of diabetes medications with the potential to cause angioedema. Both ACEI and DPP-IV inhibitors suppress enzymes involved in bradykinin catabolism, suggesting a synergistic mode of action that leads to angioedema. A review of the literature reveals only a handful of case reports published on this potential deadly medication interaction. Our case illustrates the critical importance of recognizing this rare and potentially serious side effect of combination therapy of ACEI and DPP-IV inhibitors.