Insulin degludec and insulin aspart: novel insulins for the management of diabetes mellitus

Abstract

Abstract:Patients with type 2 diabetes mellitus require insulin as disease progresses to attain or maintain glycaemic targets. Basal insulin is commonly prescribed initially, alone or with one or more rapid-acting prandial insulin doses, to limit mealtime glucose excursions (a basal-bolus regimen). Both patients and physicians must balance the advantages of improved glycaemic control with the risk of hypoglycaemia and increasing regimen complexity. The rapid-acting insulin analogues (insulin aspart, insulin lispro and insulin glulisine) all have similar pharmacokinetic and pharmacodynamic characteristics and clinical efficacy/ safety profiles. However, there are important differences in the pharmacokinetic and pharmacodynamic profiles of basal insulins (insulin glargine, insulin detemir and insulin degludec). Insulin degludec is an ultra-long-acting insulin analogue with a flat and stable glucose-lowering profile, a duration of action exceeding 30 h and less inter-patient variation in glucose-lowering effect than insulin glargine. In particular, the chemical properties of insulin degludec have allowed the development of a soluble co-formulation with prandial insulin aspart (insulin degludec/insulin aspart) that provides basal insulin coverage for at least 24 h with additional mealtime insulin for one or two meals depending on dose frequency. Pharmacokinetic and pharmacodynamic studies have shown that the distinct, long basal glucose-lowering action of insulin degludec and the prandial glucose-lowering effect of insulin aspart are maintained in the co-formulation. Evidence from pivotal phase III clinical trials indicates that insulin degludec/insulin aspart translate into sustained glycaemic control with less hypoglycaemia and the potential for a simpler insulin regimen with fewer daily injections.Keywords: basal-bolus regimen, hypoglycaemia, insulin aspart, insulin degludec, insulin degludec/insulin aspart, type 2 diabetes mellitus

A pilot study comparing the CGM-assessed glycemic profiles of patients with type 1 diabetes on insulin degludec and insulin glargine

“…Although the bolus insulin regimen used did not change throughout the study, post-supper glucose was significantly higher with InsDeg than with InsGla (Fig. 1), which agrees with previous reports [4][5][6]. It may be better to increase the bolus insulin dose at suppertime to suppress any postsupper glucose excursion when switching from InsGla to InsDeg, with the same dose used before supper.…”

“…The efficacies of basal InsGla and InsDeg (at the same dose) based on the glucose profiles of 16 patients with type 1 diabetes were investigated using CGM. InsGla has been reported to reach peak insulin action 4-5 h after injection [4,5], whereas InsDeg is reported to exhibit a flat time profile of glucose-lowering action [6]. Morning glucose was significantly lower with InsDeg than with InsGla ( Fig.…”

“…Because the correction bolus insulin amount before bed was the same during the InsDeg and the InsGla periods, InsDeg appears to exert a stronger action than InsGla around dawn. InsDeg was reported to reach peak insulin action approximately 12 h after injection [5]. The basal insulin requirement is usually increased to suppress glucose excursion at dawn (the ''dawn phenomenon'') in patients with type 1 diabetes [7].…”

Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential

“…From the classic biguanide metformin ( 1 ), to the recently Food and Drug Administration (FDA)‐approved sodium‐glucose cotransporter‐2 (SGLT‐2) inhibitor empaglifozin ( 6 ), orally available small‐molecule antidiabetic agents are daily used worldwide for the control of T2D—some of which are represented in Table . GLP‐1 analogues such as liraglutide, albiglutide, or dulaglutide are injectable alternatives, along with long‐acting insulin analogues such as insulin degludec or insulin detemir used in more advanced disease stages …”

Clinical considerations for use of insulin degludec/insulin aspart in Japanese patients

“…Current premixed insulins contain both fast-and intermediate-acting components, using intermediate-acting insulins that are protaminated to delay absorption. However, they do not provide the basal coverage seen with the newer longacting basal insulins [12]. The Treating to Target in Type 2 Diabetes (4-T) compared the 3-year efficacy and safety of different insulin regimens (prandial, biphasic, and basal) and demonstrated significantly higher median rates of hypoglycemia (5.7, 3.0, and 1.7 events per patient per year, respectively) and a greater increase in mean body weight with prandial or biphasic insulin compared with basal insulin.…”