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Pharmacological properties of faster-acting insulin aspart vs insulin aspart in patients with type 1 diabetes receiving continuous subcutaneous insulin infusion: Randomized, double-blind, crossover trial
Tim Heise, Eric Zijlstra, Leszek Nosek, Tord Rikte, Hanne Haahr
Editorial Comment by Professor Thomas Pieber
Ultra-Fast insulin analogues demonstrate improved pharmacokinetic and pharmacodynamic profiles in continuous subcutaneous insulin infusion (CSII)
Since the first attempts in the 1960’s delivery systems for continuous subcutaneous insulin infusion (CSII) have become compact, reliable, and wearable. The Diabetes Control and Complications Trial (DCCT, 1983-1993) shed light on the importance of tight control of blood glucose levels to limit microvascular complications. In turn, DCCT stimulated the development of the CSII pump as a means of delivering basal and prandial insulin; and CSII is increasingly used in patients with diabetes. Despite the introduction of short-acting insulin analogues postprandial glucose control remains a challenge, which prompted the quest of more physiologic insulin profiles for coverage of the prandial insulin need in patients with diabetes. Faster-acting insulin aspart (FIAsp) is insulin aspart in a new formulation with two added excipients, niacinamide and L-arginine. Both compounds, approved by the Food and Drug Administration (FDA) for injection, result in a faster onset of action that is twice as fast and leads to a twofold higher insulin exposure in the first 30 minutes after single injection, however, so far no data on CSII are available. In this randomized, double-blind, crossover trial Heise and colleagues evaluated the pharmacokinetic and pharmacodynamic profiles of FIAsp in patients with type 1 diabetes. All patients were on CSII and received a bolus of 0.15 U/kg of either FIAsp or insulin aspart on top of a basal rate of 0.02 U/kg body weight. Early insulin exposure in the first 30 minutes was 3fold higher with FIAsp, and glucose lowering effect was 2fold higher with FIAsp. The improved pharmacokinetic profile led to left shift of the curve, with a higher peak concentration (Cmax) and a 35 minutes earlier disappearance of insulin. Overall, this improved pharmacokinetic profile should lead to a substantial improvement of postprandial glycaemic control, currently under investigation in a phase 3 trial. Furthermore, the pharmacokinetic properties of this new formulation will open great opportunities in attempts to “close the loop” and will spur the development of the artificial pancreas, the long-term goal of modern CSII systems.