title: Saxagliptin improves glycemic control by modulating postprandial glucagon and C-peptide levels in Chinese patients with type 2 diabetes.
abstract: OBJECTIVE
  Saxagliptin reduced glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial glucose (PPG) in Asian patients with type 2 diabetes mellitus (T2DM). To understand the physiology of this effect, indices of α- and β-cell function were measured in a subpopulation of Chinese patients following a noodle mixed-meal tolerance test.
  
  
  METHODS
  Data from Chinese patients were pooled from two phase 3, 24-week studies of saxagliptin 5mg/d as monotherapy in drug-naive patients and as add-on to metformin in patients inadequately controlled with metformin alone. The end points for β- and α-cell function were change from baseline in C-peptide, insulin, and glucagon areas under the curve from 0 to 180 min (AUC0-180), insulinogenic index, and insulin sensitivity from Matsuda index after a mixed meal. Also glycemic variables, HbA1c, FPG, and PPG (AUC0-180), and homeostasis model assessment (HOMA) 2β were measured.
  
  
  RESULTS
  At 24 weeks, greater improvements in adjusted mean change from baseline HbA1c (difference vs placebo [95% CI], -0.33% [-0.50%, -0.17%], [-4 (-5.5, -1.9) mmol/mol], P<0.0001), FPG (-0.41 [-0.78, -0.03] mmol/L, P=0.03), PPG AUC0-180 (-168 [-245, -91.8] mmol min/L, P<0.0001), C-peptide AUC0-180 (19.7 [5.2, 34.2] nmol min/L, P=0.008), insulinogenic index (0.06% [0.02%, 0.09%], P=0.002), and greater suppression of glucagon secretion (glucagon AUC0-180, -322 [-493.6, -150.7] pmol min/L, P=0.0003) were observed with saxagliptin versus placebo.
  
  
  CONCLUSIONS
  In Chinese patients with T2DM, saxagliptin as monotherapy or as add-on to metformin improved glycemic control by modulating α- and β-cell function.
authors.affiliation: AstraZeneca, Mölndal, Sweden. Electronic address: mikaela.sjostrand@astrazeneca.com.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Sjöstrand
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Nayyar
authors.initials: N
authors.lastname: Iqbal
authors.affiliation: AstraZeneca, Wilmington, DE, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Lu
authors.affiliation: AstraZeneca, Wilmington, DE, USA.
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D044466:Asian People; D001786:Blood Glucose / Q000032:analysis*; D002096:C-Peptide / Q000378:metabolism*; 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; D004359:Drug Therapy, Combination; D005215:Fasting / Q000502:physiology; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects*
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D002096:C-Peptide; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; C502994:saxagliptin
keywords: China; DPP-4 inhibitors; Mixed-meal tolerance test; Saxagliptin; Type 2 diabetes mellitus