Factors Associated With Reduced Efficacy of Sitagliptin Therapy: Analysis of 93 Patients With Type 2 Diabetes Treated for 1.5 Years or Longer

BACKGROUND: Several studies have shown the effectiveness of sitagliptin, a dipeptidyl peptidase-4 inhibitor, for type 2 diabetes, with a hypoglycemic effect being demonstrated both when it is administered alone or in combination with other oral antidiabetic agents. However, there are few reports about its long-term efficacy, although medications for diabetes need to be effective over the long term. This study (as part of ASSET-K) aimed to investigate the efficacy and safety of sitagliptin when it was administered for 1.5 years or longer, and to explore factors associated with reduction of the therapeutic response. METHODS: Out of 375 patients treated with sitagliptin (50 mg/day) at Kanamori Diabetes Clinic between December 2009 and March 2012, 133 could be followed up for 72 weeks without interruption. After excluding 40 patients in whom the dosage and/or types of concomitant medications were modified during that period, the remaining 93 were included in this analysis. Clinical indices, such as blood glucose, HbA1c, and body weight, were investigated retrospectively. Compliance with diet and exercise therapy at 48 weeks was checked by a questionnaire. RESULTS: In the 93 patients analyzed (sitagliptin monotherapy, n = 9; combination therapy, n = 77; and switching from an alpha-glucosidase inhibitor or glinide, n = 7), hemoglobin A1c (HbA1c) showed a significant decrease after 24 weeks (7.70 ± 0.73% at baseline vs. 6.90 ± 0.55% at 24 weeks), but then showed a slight increase at 48 weeks. HbA1c was subsequently maintained in the same range with no significant changes until 72 weeks. A positive correlation was noted between the changes of HbA1c and body weight from 24 to 48 weeks. Compliance with diet and exercise therapy was worse in patients showing a ≥ 0.3% increase of HbA1c (n = 37) from 24 to 48 weeks than in the others (n = 56). Multiple logistic regression analysis showed that both factors were independent determinants of the increase of HbA1c from 24 weeks onward. CONCLUSIONS: Sitagliptin showed good efficacy and safety when administered for 18 months as both monotherapy and combination therapy. Inadequate compliance with diet/exercise therapy and weight again may be associated with an increase of HbA1c over time during treatment with sitagliptin.