Pharmacological properties of faster‐acting insulin aspart vs insulin aspart in patients with type 1 diabetes receiving continuous subcutaneous insulin infusion: A randomized, double‐blind, crossover trial

Abstract

AimTo evaluate the pharmacological characteristics of faster‐acting insulin aspart (faster aspart) compared with insulin aspart (IAsp) during continuous subcutaneous insulin infusion (CSII).MethodsIn this randomized, double‐blind, crossover trial, 48 men and women aged 18 to 64 years with type 1 diabetes mellitus (T1DM) received faster aspart and IAsp as a 0.15 U/kg bolus dose via CSII, on top of a basal rate (0.02 U/kg/h), in a glucose clamp setting (target 5.5 mmol/L).ResultsAfter a CSII bolus dose, the pharmacokinetic/pharmacodynamic profiles for faster aspart were left‐shifted compared with those for IAsp. For faster aspart vs IAsp, the early glucose‐lowering effect (area under the curve for glucose infusion rate [GIR]0‐30min) was approximately 2‐fold higher (least squares means 24.9 vs 11.4 mg/kg; estimated ratio faster aspart/IAsp 2.18, 95% confidence interval [CI] [1.33; 5.04]; P = .002), onset of glucose‐lowering effect (time to early 50% of maximum GIR) occurred 11.1 minutes earlier (41.1 vs 52.3 minutes; 95% CI faster aspart – IAsp [−15.4; −6.9]; P<.001), and offset of glucose‐lowering effect (time to late 50% of maximum GIR) occurred 24.0 minutes earlier (214.7 vs 238.7 minutes; 95% CI [−38.9; −9.1]; P=.002). Likewise, significantly greater early exposure and significantly earlier onset and offset of exposure were observed for faster aspart vs IAsp. Faster aspart and IAsp were both well tolerated.ConclusionsIn patients with T1DM using CSII, faster aspart better mimics the endogenous prandial insulin secretion and action than does IAsp. Faster aspart therefore has the potential to provide clinical benefits over current rapid‐acting insulins in the insulin pump setting.

Improved Postprandial Glycemic Control with Faster-Acting Insulin Aspart in Patients with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion

“…The findings of this study in terms of greater early glucose-lowering effect are in line with those recently reported by Heise et al, 23 where faster aspart and IAsp were compared in a CSII setting. While compared with s.c. administration 28 the differences in glucose-lowering effect between faster aspart and IAsp in a CSII setting appear to be more pronounced, 23 the results of the ongoing Phase 3b efficacy and safety pump trial with faster aspart will be important in terms of confirming the clinical utility of faster aspart over the longer term in a CSII setting.…”

“…While compared with s.c. administration 28 the differences in glucose-lowering effect between faster aspart and IAsp in a CSII setting appear to be more pronounced, 23 the results of the ongoing Phase 3b efficacy and safety pump trial with faster aspart will be important in terms of confirming the clinical utility of faster aspart over the longer term in a CSII setting.…”

“…22 In a recent CSII study by Heise et al, faster aspart demonstrated an almost threefold higher insulin exposure in the first 30 min and a greater glucose-lowering effect during the first 2 h following bolus dosing, compared with IAsp, while total glucose-lowering effects between treatments were similar. 23 …”

Faster-acting insulin aspart provides faster onset and greater early exposure vs insulin aspart in children and adolescents with type 1 diabetes mellitus

“…An insulin with improved pharmacological properties vs current rapid‐acting insulins may be useful in insulin pump therapy . In a CSII setting in adults with T1DM, faster aspart provided earlier onset and greater early exposure and glucose‐lowering effect vs IAsp . In children and adolescents with T1DM, CSII has advantages over multiple daily injections in terms of improved glycemic control and reduced risk of hypoglycemia .…”

A randomized, multicentre trial evaluating the efficacy and safety of fast‐acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5)

“…In a pooled analysis in participants with T1D, faster aspart demonstrated an earlier onset of appearance, a higher early insulin exposure and a greater early glucose‐lowering effect vs IAsp, when both were administered by subcutaneous injection . More pronounced clinical pharmacological improvements and a greater glucose‐lowering effect were demonstrated in people with T1D using CSII …”