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Insulin degludec/insulin aspart (IDegAsp) is a modern coformulation of ultra-long-acting basal insulin degludec, with rapid-acting insulin aspart. IDegAsp provides effective, safe, well-tolerated glycemic control, with a low risk of hypoglycemia while allowing flexibility in meal patterns and timing of administration. This consensus statement describes a pragmatic framework to identify patients who may benefit from IDegAsp therapy. It highlights the utility of IDegAsp in type 2 diabetic patients who are insulin-naive, suboptimally controlled on basal or premixed insulin, or dissatisfied with basal–bolus regimens. It also describes potential IDegAsp usage in type 1 diabetic patients.
Insulin degludec/insulin aspart (IDegAsp) is a modern coformulation of the ultra-long-acting insulin degludec (IDeg) and the rapid-acting analog insulin aspart (IAsp). IDeg and IAsp, are present in a 70:30 ratio to maintain their distinct pharmacokinetic and pharmacodynamic profile in this coformulation. Thus, IDegAsp is able to provide a safe, well-tolerated fasting as well as prandial blood glucose control.
IDegAsp is supported by a robust well-designed clinical development program known as BOOST. In phase 3a trials, IDegAsp has been studied in both type 1 and type 2 diabetes. In type 1 diabetes, IDegAsp has been compared, as part of a three-dose regimen (2 doses of IAsp and 1 dose of IDegAsp) with basal–bolus regimens consisting of maximum 4 injections/day. In type 2 diabetes, IDegAsp has been assessed as a once-daily and as a twice-daily dose for both initiation and intensification of therapy.
The pharmacokinetic and pharmacodynamic properties of IDegAsp depend on the action of its two constituents. IDeg is an ultra-long-acting basal insulin with a 25.3 h long half-life, a duration of action of 42 h, and a flat, peakless action-time profile, with low levels of variability. The risk of hypoglycemia and nocturnal hypoglycemia, in particular, is markedly reduced with IDeg as compared with comparator basal insulin. IAsp is a rapid-acting insulin analog, with an onset of action of 10–15 min, peak action at 90 min, and duration of action of 4–5 h. This suggests that IDegAsp can be administered with the main meal of the day to provide both prandial and basal control. There may be occasions when once- or twice-daily administration of IAsp is required for adequate prandial control. This can be safely achieved with two doses of IDegAsp, as IDeg does not lead to stacking due to its first-order elimination kinetics. In case a third injection is necessary for prandial glucose control, a separate dose of IAsp can be added with the third meal.
The duration of the action of IDeg (42 h), its flat action profile, and the lack of stacking allow flexibility in its timing of administration. As IDeg has been studied in forced dosage schedules with interdose gap varying from 8 to 40 h, the same flexibility can be used for IDegAsp as well. In practical terms, this implies that IDegAsp can be administered with the major meal(s) of the day, irrespective of which meal it is, provided that a 6-8 h gap is maintained between injections. This gap is required to ensure that the effect of IAsp component of the first dose is over before the next IDegAsp is injected.
In insulin-naive patients, the starting dose recommended as per label is 10 units/day. In persons on other insulins, a unit-to-unit switch is suggested as per the approved label. However, randomized controlled trials (RCTs) report 10–20% lower dose requirements with IDegAsp as compared to other available premix insulin analogs, biphasic IAsp 30.[6,7]
Based on the pharmacological properties of IDegAsp, and clinical experience gained with this molecule in three countries (Mexico, India, and Bangladesh), 10 experts from seven countries discussed and created profiles of patients with type 1 and type 2 diabetes, who would benefit from IDegAsp therapy. This work was done at a full day workshop-based advisory board meeting, held on November 29, 2015, at Vancouver, Canada. It was followed by multiple mails and telephonic discussions before the final draft was agreed upon. The shortlisted patient profiles are listed in Table 1.
In all these scenarios, interchange to IDegAsp or IDegAsp-based regimens allows effective, safe control with lesser number of injections.
This consensus statement is based on experience and backed by evidence from RCTs and pharmacokinetic/pharmacodynamic data. It provides a pragmatic framework for diabetes care professionals to help identify patients with type 1 and type 2 diabetes who may benefit from the unique properties of IDegAsp. Wider use of this molecule will help understand the utility of this modern coformulation in the management of diabetes in a better and more suitable manner.
There are no conflicts of interest.