Insulin aspart biosimilar(HEC)

Insulin aspart is a major therapeutic biomacromolecule used worldwide for the treatment of diabetes mellitus. It is administered either subcutaneously or intravenously, using infusion lines made most often from plasticized polyvinyl chloride (PVC). Unfortunately, its very nature makes it at high risk of surface interactions with the materials it can come into contact with, leading notably to greatly decreased concentrations and patient underdosing. In order to prevent this phenomenon, for which no adequate solution yet exists, in-depth knowledge of the behavior of insulin aspart at the water-solid interface is needed. The aim of this work was to shed new light on this highly problematic interaction and explain the adsorption phenomenon of insulin aspart and its phenolic excipients (phenol and metacresol) to plasticized PVC tubings from a thermodynamic point of view by combining experimental and molecular dynamics simulations. Our results proved that the hexameric form of insulin aspart possesses an important affinity for the PVC surface, to which it adsorbs nearly instantaneously to, whilst phenol and metacresol interacts with the PVC/plasticizer interface of the material. The molecular simulations of these surface interactions correlate well with the sorption processes that can be assumed to happen with the negatively charged PVC surfaces. Thermodynamic values obtained via the molecular simulation process were used to model successfully the experimental data. This combination of theoretical approaches could help us in predicting the risk of interfacial interactions in biomacromolecular systems.

Background: This study compared postprandial glycemia with faster-acting insulin aspart (FiAsp) versus insulin aspart delivered by advanced hybrid closed loop (AHCL) according to varying meal composition, time of day, and premeal bolus dose estimation in adults with type 1 diabetes. Materials and Methods: Participants received 11 weeks of insulin aspart and FiAsp in sequence, delivered by the MiniMed™ 780G AHCL algorithm, and within each period ingested 12 standardized meals. Test meals, containing 60 g of carbohydrate but varying by fat and protein content (high fat low protein [HFLP], high fat high protein [HFHP], and low fat low protein [LFLP]), were each eaten in the morning and evening and with a full bolus or 50% reduction. The primary outcome was continuous glucose monitoring time in range (%TIR; 3.9-10.0 mmol/L) 4 h postmeal for FiAsp versus insulin aspart. Results: Twelve participants (mean [standard deviation or SD] age 48 (13) years; 58% male; HbA1c 6.7 (0.7)%/50 (7) mmol/mol) were recruited. When all meal types, timing, and bolus conditions were combined, FiAsp tended to have greater glucose TIR compared with insulin aspart (mean difference = 5.17% [-0.09, 10.43]; P = 0.054), with differences most apparent for morning meals. Insulin formulation did not impact outcomes with full versus 50% premeal bolus or meal composition. HFLP meals resulted in the greatest TIR, followed by HFHP and lowest for LFLP (83.7% [19.6] vs. 74.7% [26.9] vs. 62.0% [23.1], respectively, mean [SD], P < 0.01). Conclusions: For adults with type 1 diabetes who are susceptible to morning hyperglycemia, FiAsp delivered by AHCL and higher fat content of meals may help improve postprandial glycemic outcomes. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry-ACTRN12619001340123.