Can a combination of insulin degludec/insulin aspart improve blood glucose levels?

This trial compared a combination of insulin degludec and insulin aspart with biphasic insulin aspart 30 in adults with type 2 diabetes.

Insulin is the most effective therapy for achieving glycemic (blood glucose) control in patients with type 2 diabetes, and due to the progressive nature of the disease, many type 2 diabetes patients will become candidates for such a therapy. Therapy may eventually consist of a basal insulin (long-acting insulin that releases over 8–24 hours, providing background levels of insulin) and a prandial insulin (rapid-acting insulin that is quickly absorbed to provide the level of insulin required at mealtimes).

Comprising of 70% insulin degludec (Tresiba) and 30% insulin aspart (NovoLog), IDegAsp (Ryzodeg) is the first soluble combination product of a basal insulin with an ultralong duration of action and a rapid-acting insulin in a single injection. In this trial, IDegAsp is compared to biphasic IAsp 30 (NovoMix; a mixture consisting of 30% insulin aspart that is rapid-acting and 70% insulin aspart that is intermediate-acting).

447 patients with type 2 diabetes were randomly assigned to receive either IDegAsp or biphasic IAsp 30. 224 patients received twice daily IDegAsp while 223 received twice daily biphasic IAsp 30 with or without oral antidiabetic agents for 26 weeks.

After 26 weeks of treatment, the observed average HbA1c levels (a measurement of average blood glucose levels over the past 3 months) decreased from 8.3% at the beginning of the study to 7.1% with IDegAsp, and from 8.4% to 7.1% with biphasic IAsp 30. 50.4% of the IDegAsp group and 48.6% of the biphasic IAsp 30 group achieved a HbA1c level of below 7%. The odds of achieving this target without hypoglycemic (dangerously low blood glucose level) episodes during the last 12 weeks were 60% higher for the IDegAsp group compared to the biphasic IAsp 30.

Fasting plasma glucose decreased from an average of 8.9 mmol/L to 5.8 mmol/L in the IDegAsp group and from 8.6 mmol/L to 6.8 mmol/L in the biphasic IAsp 30 group. 37.9% of the IDegAsp group reached the self-measured plasma glucose pre-breakfast target of less than 5 mmol/L compared with 23% of the biphasic Asp 30 group.

Patients in the IDegAsp group experienced an average of 1.7kg weight gain compared to 2.2kg in the biphasic IAsp 30 group. The average daily insulin dose by the end of the study was 1.08 units/kg for the IDegAsp group and 1.2 units/kg for the biphasic IAsp 30 group.

Confirmed hypoglycemia (plasma glucose of less than 3.1 mmol/L) was reported for 66.1%of the IDegAsp group and 68.9% of the biphasic IAsp 30 group. Superiority of IDegAsp versus biphasic IAsp 30 was demonstrated with a 32% reduction in confirmed hypoglycemic episodes. A 73% reduction in night-time confirmed hypoglycemia was observed for IDegAsp compared to biphasic IAsp 30. 3.1% of the IDegAsp group experienced severe hypoglycemia compared to 7.2% of the biphasic IAsp 30 group.

65.6% of the IDegAsp group experienced adverse events compared to 63.1% of the biphasic IAsp 30 group. The most common events were nasopharyngitis (common cold), upper-respiratory tract infection and headache.

The authors concluded that IDegAsp twice-daily effectively improved HbA1c and fasting plasma glucose levels with fewer hypoglycemic episodes versus twice-daily biphasic IAsp 30.