PurposeTreatment with dipeptidyl peptidase 4 (DPP-4) inhibitors may have responders or nonresponders. However, agreement on the effects of patient background and/or contributory factors that have a negative effect on the efficacy of DPP-4 inhibitors is lacking. The aim of the present study was to investigate the effect of resistance factors on the clinical efficacy of sitagliptin (SITA) for patients with type 2 diabetes. MethodsWe performed a retrospective study based on the medical records of patients who were treated with SITA alone (SITA-A; n = 16), a combination of a sulfonylurea (SU) without a change in dose and add-on SITA (SU + SITA; n = 29), SITA alone after the discontinuation of premedication with antidiabetic agents (SITA-AD; n = 18), or a combination of an SU with a dose reduction and SITA (L-SU + SITA; n = 17). Multivariate logistic regression analysis was employed to estimate the influence of resistance factors on hemoglobin (Hb) A1c lowering by SITA treatment for 3 months. FindingsThe HbA1c levels were significantly lower after 3-month treatment with SITA-A (6.3% [0.2%]), SU + SITA (7.1% [0.2%]), and L-SU + SITA (6.6% [0.2%]), but not with SITA-AD (6.3% [0.2%]), than baseline levels before treatment. Multivariate logistic regression analysis established that a decreased efficacy of SITA was markedly related to baseline HbA1c levels of ≥7.5% and dyslipidemia. ImplicationsThese results suggest that checking for the presence or absence of resistance factors, including elevated HbA1c levels and dyslipidemia, may contribute to the appropriate usage of SITA.