title: Impact of treatment with saxagliptin on glycaemic stability and β-cell function in the SAVOR-TIMI 53 study.
abstract: OBJECTIVE
  To study the effects of saxagliptin, a dipeptidyl peptidase-4 inhibitor, on glycaemic stability and β-cell function in the SAVOR-TIMI 53 trial.
  
  
  METHODS
  We randomized 16,492 patients with type 2 diabetes (T2D) to saxagliptin or placebo, added to current antidiabetic medications, and followed them for a median of 2.1 years. Glycaemic instability was defined by: (i) a glycated haemoglobin (HbA1c) increase of ≥ 0.5% post-randomization; (ii) the initiation of new antidiabetic medications for ≥ 3 months; or (iii) an increase in dose of oral antidiabetic medication or ≥ 25% increase in insulin dose for ≥ 3 months. β-cell function was assessed according to fasting homeostatic model 2 assessment of β-cell function (HOMA-2β) values at baseline and at year 2 in patients not treated with insulin.
  
  
  RESULTS
  Compared with placebo, participants treated with saxagliptin had a reduction in the development of glycaemic instability (hazard ratio 0.71; 95% confidence interval 0.68-0.74; p < 0.0001). In participants treated with saxagliptin compared with placebo, the occurrence of an HbA1c increase of ≥ 0.5% was reduced by 35.2%; initiation of insulin was decreased by 31.7% and the increases in doses of an oral antidiabetic drug or insulin were reduced by 19.5 and 23.5%, respectively (all p < 0.0001). At 2 years, HOMA-2β values decreased by 4.9% in participants treated with placebo, compared with an increase of 1.1% in those treated with saxagliptin (p < 0.0001).
  
  
  CONCLUSIONS
  Saxagliptin improved glycaemia and prevented the reduction in HOMA-2β values. Saxagliptin may reduce the usual decline in β-cell function in T2D, thereby slowing diabetes progression.
authors: The Diabetes Unit, Hadassah University Hospital, Jerusalem, Israel; The Endocrine Service, Hadassah University Hospital, Jerusalem, Israel.
authors: G
authors: G
authors: Leibowitz
authors: A
authors: A
authors: Cahn
authors: D L
authors: DL
authors: Bhatt
authors: B
authors: B
authors: Hirshberg
authors: O
authors: O
authors: Mosenzon
authors: C
authors: C
authors: Wei
authors: G
authors: G
authors: Jermendy
authors: W H-H
authors: WH
authors: Sheu
authors: J L
authors: JL
authors: Sendon
authors: K
authors: K
authors: Im
authors: E
authors: E
authors: Braunwald
authors: B M
authors: BM
authors: Scirica
authors: I
authors: I
authors: Raz
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004151:Dipeptides / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human; C502994:saxagliptin
keywords: clinical trial; dipeptidyl peptidase-4 inhibitor; glycaemic control; type 2 diabetes; β cell