Combined Insulin Degludec and Aspart in Insulin-Naïve Patients

OCTOBER 26, 2016
Patients with type 2 diabetes eventually need insulin therapy as their disease progresses. The American Diabetes Association recommends basal-only therapy initially, with the addition of bolus meal-time insulin as needed. However, recent research supports starting patients on combined basal-bolus regimens to control blood sugar regardless of added hypoglycemia risk.
A combined basal insulin degludec (70%) and rapid-acting insulin aspart (30%) product is now available as a single injection pen. Insulin degludec has less response variability and nocturnal hypoglycemia than insulin glargine in insulin-naïve patients. These benefits should persist with use of the combination product because the individual components do not affect each other’s pharmacokinetics.

A new study’s results suggest that insulin glargine therapy causes more nighttime hypoglycemia and that combined insulin degludec/insulin aspart causes more daytime hypoglycemia.1

The trial was open-label, parallel-grouped, and treat-to-target with patients randomized to receive insulin degludec/insulin aspart each morning or insulin glargine once daily. The researchers measured change in hemoglobin A1c 26 and 52 weeks after initiation.

The included patients had been diagnosed with type 2 diabetes at least 6 months prior to enrollment, they were insulin-naïve, and they’d been taking an oral antidiabetic product for at least 3 months with an A1c of 7.5% to 11%. The study excluded patients who had received a GLP-1 agonist or thiazolidinedione in the 3 months prior to initiation.

Combined insulin degludec/insulin aspart therapy was noninferior to insulin glargine to reduce hemoglobin A1c over 26 and 52 weeks in insulin-naïve patients inadequately responsive to metformin therapy. Insulin degludec/insulin aspart had a greater risk of overall hypoglycemia due to the rapid-acting effects of insulin aspart and the regimen’s morning administration. Bedtime administration may have caused the insulin glargine-induced nocturnal hypoglycemia. The study authors attribute the nocturnal hypoglycemia to insulin glargine’s less flat action profile.

The combined insulin patients received more insulin than did the insulin glargine patients because the combined product has larger dose increments. The insulin degludec/insulin aspart patients gained more body weight over the study period and achieved similar fast blood glucose control with less basal insulin on average.

Another study’s results found that administering insulin degludec/insulin aspart with the largest meal of the day curtails hypoglycemia without impacting fasting blood sugar control or hemoglobin A1c reduction. The half-life of insulin degludec is twice as long as insulin glargine’s and regulates post-dinner hyperglycemia more tightly than insulin glargine when given at dinner.2

Combined basal-bolus insulin degludec/insulin aspart is noninferior to basal-only insulin glargine to control fast blood glucose and hemoglobin A1c in insulin-naïve type 2 diabetes patients. Providers should recommend administering the combined insulin product with the largest meal of the day to prevent daytime hypoglycemia.

  1. Kumar A, et al. Efficacy and safety of once-daily insulin degludec/insulin aspart versus insulin glargine (U100) for 52 weeks in insulin-naïve patients with type 2 diabetes: a randomized controlled trial. PLOS ONE. 2016;11(10):e0163350.
  2. Onishi Y, et al. Superior glycaemic control with once-daily insulin degludec/insulin aspart versus insulin glargine in Japanese adults with type 2 diabetes inadequately controlled with oral drugs: a randomized, controlled phase 3 trial. Diabetes Obes Metab. 2013;15(9):826-832.

Daniel Holland, PharmD
Daniel Holland, PharmD
Daniel Holland, PharmD, is a graduate and medical writer from the University of Connecticut School of Pharmacy. Connect with him on LinkedIn or at