Letter: Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2015;39:342-7)

Corresponding author: Ye An Kim Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, 152 Teheran-ro, Gangnam-gu, Seoul 06236, Korea E-mail: [email protected] Dipeptidyl peptidase-4 (DPP-4) inhibitor is one of the widely used diabetic medications these days. In clinical practice, some patients respond more effectively to this drug and show better glycemic improvement. Several studies [1-4] analyzed the predictors of response to DPP-4 inhibitors, however the results were somewhat inconsistent. The discrepancy might be due to the different definition of efficacy predictors and heterogeneity of study population. In this article entitled “Predictive factors for efficacy of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus,” Yagi et al. [5] evaluated the predictive factors for the efficacy of DPP-4 inhibitors based on the change of glycosylated hemoglobin (HbA1c) after 12 months of treatment. They described the predictors to be a decrease in HbA1c level after 3 months of treatment, a high baseline HbA1c level, a low baseline body mass index, and no history of coronary artery disease (CAD). This article is interesting, especially in that the longterm effects of DPP-4 inhibitors on glycemic control could be predicted by the short term response, which might make it easier to identify the good responders to DPP-4 inhibitors. Although there are some clinical significances, some points need to be clarified. First, the criteria for DPP-4 inhibitor add-on therapy needs to be clarified better in this study. The study patients aged 68.3±35.8 years old, and baseline HbA1c were 7.5%±1.3%. Initially, 36.6% of patients already had HbA1c <7% when DPP4 inhibitors are added on. Considering that the patients were relatively old with mild elevated HbA1c level, the reason for additional DPP-4 inhibitors might be helpful to understand and validate the efficacy of DPP-4 inhibitors. In addition, a majority of patients have already been treated with other anti-diabetic drugs. Forty-four percent of patients used α-glucosidase inhibitors, 32.5% for sulfonylurea, and 15.2% for biguanides. In these patients, the reason for additional DPP-4 inhibitor instead of the dose increment of baseline drugs could be informative. Second, combination therapy of other anti-diabetic drugs might affect glucose metabolism and exert confounding effects. A previous study has reported that combination treatment of alogliptin and voglibose increased plasma active glucagon-like peptide-1 (GLP-1) levels and pancreatic insulin content synergistically in db/db mice [6]. Another study showed that a combination of miglitol and sitagliptin effectively attenuate postprandial hyperglycemia with various patterns of insulin, glucagon, and GLP-1 release, suggesting that individual hormone-related glycemic responses to the DPP-4 inhibitors and α-glucosidase inhibitor are complex and multifactorial [7]. Synergistic effect of sulfonylurea and DPP-4 inhibitor has been suggested, because some patients showed dramatic glycemic improvement after this combination therapy [8]. Sulfonylurea added to DPP-4 inhibitor might potentiate insulin secretion by activating exchange protein activated by cyclic AMP 2 (Epac2) [9]. There are substantial synergistic or Letter