Clinical Effects of Exposure to DPP-4 Inhibitors as Reported to the National Poison Data System

Abstract

DPP-4 inhibitors (sitagliptin, saxagliptin, and linagliptin) are approved for the treatment of diabetes. They are considered safe due to their hyperglycemia dependent mechanism of action. We examined all isolated exposures to DPP-4 inhibitors reported to the National Poison Database System since 2006 to determine if significant toxicity occurs after exposure with attention to pediatric and intentional overdoses. NPDS data regarding DPP-4 ingestions in all age groups between January 2006 and March 2013 was collected. Cases were reviewed, and the following inclusion criteria applied: (1) reported ingestion of a DPP-4 inhibitor and (2) known clinical outcome. Exclusion criteria included the following: (1) exposure to more than a single substance, (2) no known outcome, and (3) clinical outcome judged to be unrelated to the exposure. One thousand four hundred seventy-six cases were reviewed while 826 were excluded. Of 650 included cases, 562 developed no clinical effects. Mild effects were noted in 77. There were no deaths. Moderate/major effect cases were investigated: two medication-naive nondiabetic individuals with accidental exposures developed clinically significant hypoglycemia requiring treatment. One diabetic patient on a DPP-4 inhibitor developed prolonged hypoglycemia requiring admission and continuous exogenous dextrose. Of 650 included exposures to DPP-4 inhibitors, 639 (98.3%) had either no or minor clinical effects. Three resulted in clinically significant hypoglycemia requiring intervention. None of the moderate or major clinical outcomes were the result of intentional overdoses for the purpose of self-injury. No exploratory ingestions resulted in moderate or major effects. Based on this data, exposure to DPP-4 inhibitors may rarely result in clinically significant hypoglycemia.