title: Blood Glucagon Levels Predict the Hemoglobin A1c Response to Saxagliptin in Patients with Type 2 Diabetes Inadequately Controlled with Metformin.
abstract: BACKGROUND
  Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as second-option medications when metformin fails. Variance of the glycated hemoglobin (HbA1c) response to DPP-4 inhibitions in patients with type 2 diabetes mellitus (T2DM) has been observed, but the characteristics which predict the response to DPP-4 inhibitor therapy are unclear. The aim of this study was to investigate the characteristics of α- and β-cell functions which might predict the efficacy of saxagliptin and facilitate personalization of treatment.
  
  
  METHODS
  We studied 60 patients with T2DM who had inadequate glycemic control [HbA1c7.0-13.0% (53-119 mmol/mol)) with metformin alone. The patients were treated with saxagliptin (5 mg, daily) and metformin (1000-2000 mg as former) for 12 weeks. Oral glucose tolerance tests were carried out at baseline and endpoint to evaluate α- and β-cell functions, and blood C-peptide, insulin, glucagon levels were tested. Blood glucose, HbA1c and weight were also observed.
  
  
  RESULTS
  Significant reduction of weight, HbA1c and glucagon was observed after 12-week treatment, while C-peptide, insulin and homeostasis model assessment-β increased (P < 0.05). Linear regression and receiver operating characteristic analysis showed that baseline HbA1c and 30 min-glucagon were correlated with the HbA1c response to saxagliptin, while the weight loss was correlated with gender, age and fasting-insulin level. Further analysis showed the 30 min-glucagon of 49.1 pmol/L was the optimal cutoff value to predict the efficacy of saxagliptin.
  
  
  CONCLUSIONS
  Saxagliptin added to metformin significantly improved glycemic control and α- and β-cell function. Blood glucagon level was a good predicting factor for the HbA1c response to saxagliptin, and it will help appropriate patient selection.
  
  
  BACKGROUND
  Chinese Clinical Trial Register identifier, ChiCTR-PPR-15007045.
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Feng-Fei
authors.initials: FF
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Bing-Li
authors.initials: BL
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. suxiaofeifei@126.com.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Su
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. majianhua196503@126.com.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ma
keywords: Efficacy; Glucagon; Saxagliptin; T2DM