sitagliptin-phosphate and Angioedema

Dipeptidyl peptidase-4 (DPP-4) plays a minor role in degrading vasoactive peptides that cause angioedema when angiotensin-converting enzyme (ACE) is present and fully functional. This study investigated the association between DPP-4 inhibitors (DPP-4Is) and angioedema, including cases where the concomitant use of ACE inhibitors (ACEIs) was absent. We obtained data from the US Food and Drug Administration Adverse Event Reporting System and performed a disproportionality analysis, using the reporting odds ratio (ROR) and information component (IC) for signal detection in patients aged ≥ 40 years, stratified by age group and sex. No signal was detected for DPP-4Is when the entire dataset was analyzed. However, a signal was detected for the entire female subset group, the three stratified female groups aged ≥ 60 years, and males in their 40 s. After excluding the data of concomitant ACEI users, most ROR and IC values were lower and significant only for females in their 60 s and males aged ≥ 80 years. Regarding individual DPP-4Is signals, those detected for saxagliptin and sitagliptin in some age groups disappeared after excluding the data of ACEI users. Notably, linagliptin was the only DPP-4I where signals were detected in most female groups, regardless of age and without concomitant ACEI use. Our findings suggest that some DPP-4Is were associated with a higher reporting of angioedema as per age and sex, even in the absence of concomitant ACEI use.

Topics: Adult; Aged; Aged, 80 and over; Angioedema; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Male; Middle Aged; Pharmacovigilance; Sitagliptin Phosphate; United States; United States Food and Drug Administration

Topics: Angioedema; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Male; Middle Aged; Sitagliptin Phosphate

New concepts of idiopathic and iatrogenic angioedema underline the role of bradykinin, and the importance of catabolizing enzymes. A case is described of Angiotensin converting enzyme inhibitor (ACEi) and sitagliptin induced angioedema, where AO attacks decreased after the withdrawal of lisinopril but resolved only after the withdrawal of sitagliptin, an inhibitor of dipeptylpeptidase IV. ACE, aminopeptidase P and carboxypeptidase N were decreased down to 17%, 42%, 64% of median references values, and remained low one year after the interruption of these drugs: 56%, 28% and 50%, respectively. The combined deficiency of APP and CPN might enhance the inhibiting effect of the DPP IV inhibitor. The fact that this triple deficiency remained latent before and after the treatment indicates that searching for latent enzyme deficiencies should be carried out when there is intention to treat with a combination of drugs interfering with the bradykinin metabolism.

Topics: Amino Acid Metabolism, Inborn Errors; Aminopeptidases; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Dipeptidyl-Peptidase IV Inhibitors; Down-Regulation; Drug Interactions; Humans; Iatrogenic Disease; Lisinopril; Lysine Carboxypeptidase; Male; Middle Aged; Peptidyl-Dipeptidase A; Polypharmacy; Pyrazines; Risk Factors; Sitagliptin Phosphate; Time Factors; Triazoles

Topics: Angioedema; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Middle Aged; Pyrazines; Sitagliptin Phosphate; Triazoles

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Blood Coagulation Factors; Bradykinin; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypertension; Laryngeal Diseases; Male; Perindopril; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles

Topics: Aged; Angioedema; Angiotensin II Type 1 Receptor Blockers; Biphenyl Compounds; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Irbesartan; Pyrazines; Sitagliptin Phosphate; Tetrazoles; Treatment Outcome; Triazoles