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.