title: Combination of Saxagliptin and Metformin Is Effective as Initial Therapy in New-Onset Type 2 Diabetes Mellitus With Severe Hyperglycemia.
abstract: BACKGROUND
  The efficacy/safety of combination oral agents in those with stable newly diagnosed type 2 diabetes (T2DM) with severe hyperglycemia is unknown.
  
  
  OBJECTIVE
  The objective of the study was to assess glycemic and β-cell outcomes of two oral regimens.
  
  
  METHODS
  This was an open-label, randomized controlled trial with patients enrolled from 2011 through 2014 and followed up for 12 weeks.
  
  
  METHODS
  The study was conducted at a major public hospital in Chicago.
  
  
  METHODS
  One hundred adults with newly diagnosed T2DM and severe hyperglycemia (300-450 mg/dL) participated in the study.
  
  
  METHODS
  One hundred patients were randomized to receive Kombiglyze XR (saxagliptin 5 mg/metformin 2000 mg) daily (K group) vs glipizide XL 10 mg daily (G group).
  
  
  METHODS
  The measure was to maintain fasting/premeal glucose of less than 300 mg/dL up to 6 weeks and less than 250 mg/dL after 6 weeks until study end, and to have no return acute care-site visits. Those not meeting criteria were discontinued. Other outcomes included continuous glucose monitoring (CGM) and β-cell function estimates at start and study end.
  
  
  RESULTS
  Baseline characteristics and primary outcome (K group 94%, G group 98%) were similar in both groups. The enrollment glucose (K group 343 mg/dL, G group 341 mg/dL) and glycated hemoglobin (K group 10.8%, G group 11%) declined by week 12 (K group 137 mg/dL, G group 129 mg/dL, and K group 6.8%, G group 6.9%), respectively. Homeostasis model assessment to assess basal insulin secretion and early insulin response improved severalfold (K group ×5.8, G group ×5.9, and K group ×9.5, G group ×13.1). In follow-up, the incidence of hypoglycemia was lower in the K group (self-monitored blood glucose: K group 8.0%, G group 24%; CGM: K group 20%, G group 46.5%) as were the number of episodes of hypoglycemia (self-monitored blood glucose: K group 4 in 12 weeks, G group 27 in 12 weeks; CGM: K group 0.28 per 24 h, G group 0.31 per 24 h).
  
  
  CONCLUSIONS
  Kombiglyze XR and glipizide XL are efficacious in improving glycemia and β-cell function in stable newly diagnosed T2DM with severe hyperglycemia. The K group had less hypoglycemia. These results suggest that certain oral medications could be appropriate alternatives in treating severe hyperglycemia.
authors.affiliation: Division of Endocrinology (A.A., D.L., L.F.), Cook County Health and Hospitals System, Chicago, Illinois 60612; and Department of Medicine (A.A., L.F.), Rush University Medical Center, Chicago, Illinois 60612.
authors.forename: Ambika
authors.initials: A
authors.lastname: Amblee
authors.affiliation: Division of Endocrinology (A.A., D.L., L.F.), Cook County Health and Hospitals System, Chicago, Illinois 60612; and Department of Medicine (A.A., L.F.), Rush University Medical Center, Chicago, Illinois 60612.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lious
authors.affiliation: Division of Endocrinology (A.A., D.L., L.F.), Cook County Health and Hospitals System, Chicago, Illinois 60612; and Department of Medicine (A.A., L.F.), Rush University Medical Center, Chicago, Illinois 60612.
authors.forename: Leon
authors.initials: L
authors.lastname: Fogelfeld
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004151:Dipeptides / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; C502994:saxagliptin