Abstract
INTRODUCTION: In a preceding trial comparing two different titration schemes, insulin degludec/insulin aspart (IDegAsp) showed good efficacy for achieving HbA(1c) <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). METHOD: A 26-week, randomized, open-label, phase 3b, treat-to-target trial in which 40 patients with T2D who had not reached target HbA(1c) ≤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 HbA(1c) was 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 HbA(1c) from 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 HbA(1c) <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. CONCLUSION: When used as intensification regimens in patients who failed to achieve target HbA(1c) during 26-week IDegAsp BID treatment, HbA(1c) improvements 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. FUNDING: Novo Nordisk. CLINICALTRIALS. GOV IDENTIFIER: NCT01814137.