title: Intensification of IDegAsp Twice Daily (Adding Insulin Aspart vs. Switching To Basal-Bolus): Exploratory Randomized Trial in Type 2 Diabetes.
abstract: BACKGROUND
  In a preceding trial comparing two different titration schemes, insulin degludec/insulin aspart (IDegAsp) showed good efficacy for achieving HbA1c<7% when administered twice daily (BID) in patients with uncontrolled type 2 diabetes (T2D). However, poor glycemic control persisted in a minority of patients. The current exploratory trial investigated the efficacy and safety of intensifying IDegAsp BID treatment in these patients by either adding a once-daily (OD) bolus injection of insulin aspart (IAsp) or by switching to a basal-bolus regimen of insulin degludec (IDeg) plus IAsp taken three times a day (TID).
  
  
  METHODS
  A 26-week, randomized, open-label, phase 3b, treat-to-target trial in which 40 patients with T2D who had not reached target HbA1c≤7.0% following previous 26-week treatment intensification with IDegAsp BID ±3 oral antidiabetic agents (OADs) were randomized (1:1) to receive IDegAsp BID + IAsp OD (n = 20) or IDeg OD + IAsp TID (n = 20).
  
  
  RESULTS
  Mean baseline HbA1cwas 7.9% in the IDegAsp BID + IAsp OD group and 7.7% in the IDeg OD + IAsp TID group. After 26 weeks, the estimated mean change in HbA1cfrom baseline was 0.05% points in the IDegAsp BID + IAsp OD group and -0.49% points for IDeg OD + IAsp TID: estimated treatment difference (ETD) [95% confidence interval] 0.54% [0.09; 0.99], p = 0.021. Few achieved HbA1c<7% in IDegAsp BID + IAsp OD (four patients) and IDeg OD + IAsp TID groups (five patients). Fasting plasma glucose, hypoglycemia, and adverse events were similar between groups.
  
  
  CONCLUSIONS
  When used as intensification regimens in patients who failed to achieve target HbA1cduring 26-week IDegAsp BID treatment, HbA1cimprovements were numerically greater with IDeg OD + IAsp TID compared with IDegAsp BID + IAsp OD. No new safety issues were identified. However, the small, selective sample means clinical generalizations should be made with caution.
  
  
  BACKGROUND
  Novo Nordisk. CLINICALTRIALS.
  NCT01814137.
authors.affiliation: School of Medical Sciences Universiti Sains Malaysia, 16150, Kota Bharu, Kelantan, Malaysia. wanmohd@usm.my.
authors.forename: Wan Mohamaed Wan
authors.initials: WM
authors.lastname: Bebakar
authors.affiliation: Meridien Research, 5700 E State Road 64, Bradenton, FL, 34208, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Chaykin
authors.affiliation: Novo Nordisk A/S, Vandtaarnsvej 114, 2860, Søborg, Denmark.
authors.forename: Malene Lundgren
authors.initials: ML
authors.lastname: Hersløv
authors.affiliation: Novo Nordisk A/S, Vandtaarnsvej 114, 2860, Søborg, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Rasmussen
keywords: Glycemic control; Insulin degludec/insulin aspart; Insulin intensification