Add-On Sitagliptin Therapy for Insulin-Treated Type 2 Diabetes: An Analysis of Hemoglobin A1c and Other Variables Using ASSIST-K Follow-Up Data

Background: Sitagliptinwas the first dipeptidyl peptidase-4 (DPP-4) inhibitor approved in Japan. Its efficacy and safety have been demonstrated, both as monotherapy and in combination with oral antidiabetic agents or insulin. However, reduction of hemoglobin A1c (HbA1c) by sitagliptinis insufficient in some patients. Therefore, data from an observational study of sitagliptinas add-on therapy to insulin in patients with type 2 diabetes (ASSIST-K) were used to conduct factoranalysis of the 12-month changes in HbA1c, body weight, estimated glomerular filtration rate (eGFR), and adverse events (AEs). Methods: At member institutions of Kanagawa Physicians Association specializing in diabetes, outpatients with type 2 diabetes receiving insulin were followed for 12 months after addition of sitagliptin. The HbA1c (National Glycohemoglobin Standardization Program), blood glucose (fasting/postprandial), body weight, eGFR, and AEs were evaluated at each specified time. Multivariate analysis was performed by using sex and age as explanatory variables and the following response variables: the change in HbA1c, body weight, or eGFR after 12 months of sitagliptintreatment, and occurrence of AEs. Results: Of 1,168 patients registered in the ASSIST-K study, 412 patients were included in this analysis, excluding those not receiving insulin before sitagliptin, those in whom the 12-month change in HbA1c could not be calculated, and those with missing data on explanatory variables. There was a significant decrease in HbA1c and eGFR, but no significant change in body weight. AEs observed in > 10 patients were severe hypoglycemia (14 patients, 3.4%) and constipation (13 patients, 3.2%). Factor analysis revealed the following points: 1) Concurrent dyslipidemiaand baselineHbA1c influenced the 12-month change in HbA1c; 2) Baselinebody mass index and HbA1c influenced the 12-month change in body weight; and 3) Concurrent dyslipidemia, baseline sulfonylureatreatment, baselinebody mass index, and baselineeGFR influenced the 12-month change in eGFR. In addition, the risk of severe hypoglycemia or constipation was significantly influenced by baselineHbA1c. Conclusions: Patients with type 2 diabetes showing higher HbA1c levels after add-on sitagliptintherapy had concurrent dyslipidemiaand a lower baselineHbA1c. Severe hypoglycemia or constipation was more likely to occur in patients with a low baselineHbA1c. J Endocrinol Metab. 2018;8(6):126-138 doi: https://doi.org/10.14740/jem540