BACKGROUND: Meta-analyses of randomized clinical trials have reported that dipeptidyl peptidase IV (DPP-4) inhibitors are well tolerated and that the incidence of hypoglycemia with the use of DPP-4 inhibitors is similar to that observed with placebos. However, in general, provider-oriented methods using medical record reviews offer lower rates of non-serious, symptomatic adverse drug reactions (ADRs) than patient-oriented methods. Moreover, severe hypoglycemia occurred in three clinical trials using sitagliptin, but in two of these trials this phenomenon has been previously described only in the drug application data in the US. OBJECTIVE: The aim of this study was to assess the profile of patient-reported symptomatic ADRs under DPP-4 inhibitor therapy and to detect risk factors for hypoglycemic and non-hypoglycemic adverse symptoms in daily clinical practice. METHODS: We analyzed a subpopulation of participants in the Drug Event Monitoring (DEM) project of the Japan Pharmaceutical Association. An anonymous survey was conducted in February 2012 to assess the self-perception of adverse symptoms during a median 28 (4-88) days after the last prescription of DPP-4 inhibitors by means of interviews of pharmacists using structured questionnaires. RESULTS: A total of 864 males and 686 females were included. The prescribed DPP-4 inhibitors included sitagliptin (75.4 %), alogliptin (15.5 %), vildagliptin (8.8 %) and linagliptin (0.3 %). Mild hypoglycemic symptoms were reported by 34 individuals (2.2 %) receiving monotherapy of sitagliptin (10/402) or alogliptin (3/65), or combination therapy of sitagliptin (15/767) or alogliptin (6/176) with other hypoglycemic agents. In the multiple regression model, hypoglycemic symptoms were found to be significantly associated with liver disease, female sex and alcohol consumption more than three times per week. Non-hypoglycemic symptoms were reported by 57 individuals (3.7 %), the most common symptoms of which were gastrointestinal symptoms (2.1 %). Combination therapy was only found to be associated with nonhypoglycemic symptoms. CONCLUSIONS: The present study suggested that hypoglycemic symptoms under therapy with sitagliptin or alogliptin may be associated with liver disease, female sex and alcohol consumption, all of which are potentially capable of leading to poor gluconeogenesis because they decrease the counter-regulatory hormonal responses to hypoglycemia.
BACKGROUND: Meta-analyses of randomized clinical trials have reported that dipeptidyl peptidase IV (DPP-4) inhibitors are well tolerated and that the incidence of hypoglycemia with the use of DPP-4 inhibitors is similar to that observed with placebos. However, in general, provider-oriented methods using medical record reviews offer lower rates of non-serious, symptomatic adverse drug reactions (ADRs) than patient-oriented methods. Moreover, severe hypoglycemia occurred in three clinical trials using sitagliptin, but in two of these trials this phenomenon has been previously described only in the drug application data in the US. OBJECTIVE: The aim of this study was to assess the profile of patient-reported symptomatic ADRs under DPP-4 inhibitor therapy and to detect risk factors for hypoglycemic and non-hypoglycemic adverse symptoms in daily clinical practice. METHODS: We analyzed a subpopulation of participants in the Drug Event Monitoring (DEM) project of the Japan Pharmaceutical Association. An anonymous survey was conducted in February 2012 to assess the self-perception of adverse symptoms during a median 28 (4-88) days after the last prescription of DPP-4 inhibitors by means of interviews of pharmacists using structured questionnaires. RESULTS: A total of 864 males and 686 females were included. The prescribed DPP-4 inhibitors included sitagliptin (75.4 %), alogliptin (15.5 %), vildagliptin (8.8 %) and linagliptin (0.3 %). Mild hypoglycemic symptoms were reported by 34 individuals (2.2 %) receiving monotherapy of sitagliptin (10/402) or alogliptin (3/65), or combination therapy of sitagliptin (15/767) or alogliptin (6/176) with other hypoglycemic agents. In the multiple regression model, hypoglycemic symptoms were found to be significantly associated with liver disease, female sex and alcohol consumption more than three times per week. Non-hypoglycemic symptoms were reported by 57 individuals (3.7 %), the most common symptoms of which were gastrointestinal symptoms (2.1 %). Combination therapy was only found to be associated with nonhypoglycemic symptoms. CONCLUSIONS: The present study suggested that hypoglycemic symptoms under therapy with sitagliptin or alogliptin may be associated with liver disease, female sex and alcohol consumption, all of which are potentially capable of leading to poor gluconeogenesis because they decrease the counter-regulatory hormonal responses to hypoglycemia.