Injection speed had no effect on injection pain, whereas higher injection volumes caused more pain. The results of this study may be of value for guiding patients to use the appropriate injection site and technique to reduce their injection pain. Furthermore, these findings may have important implications for the development of new injection devices and drug formulations for clinical practice.

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The hyperinsulinaemic-euglycaemic glucose clamp has always been regarded as the "gold standard" for the assessment of pharmacodynamic (PD) properties of insulin preparations; however, there has been controversy over a variety of methodogical details, such as study population, dosing time and the initial stabilization of blood glucose (BG) concentrations at the clamp target level, among clamp groups. As the impact of these details on PD results is unclear, the present review provides an overview of different methodological approaches for both the man- However, even before this, clamp experts had discussed and sometimes disagreed on methodological details, 5 making it difficult to assess the PD results of glucose clamp studies for non-experts, particularly when these results differed between clamp groups. It might therefore be time to review both the strengths and the limitations of the clamp technique, addressing the most important methodological issues and discussing their potential impact on PD outcomes. | GLUCOSE CLAMP STUDIES: PRINCIPLE AND BASIC CONSIDERATIONSThe principle of the PD glucose clamp is quite simple 1 : the blood glucose (BG)-lowering effect of an insulin is antagonized by glucose

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.

BackgroundAbsorption of current rapid-acting insulins is too slow for patients with diabetes mellitus to achieve optimal postprandial glucose control. Faster-acting insulin aspart (faster aspart) is insulin aspart in a new formulation with faster early absorption. We compared the pharmacokinetic/pharmacodynamic properties of faster aspart and insulin aspart across a clinically relevant dose range.MethodsIn this randomised, double-blind, crossover trial, 46 subjects with type 1 diabetes mellitus received single subcutaneous doses of faster aspart and insulin aspart at 0.1, 0.2 (repeated three times to estimate within-subject variability) and 0.4 U/kg in a euglycaemic clamp setting (target 5.5 mmol/L).ResultsConsistently for the three doses, faster aspart demonstrated faster onset and greater early absorption and glucose-lowering effect versus insulin aspart. Across all three doses, onset of appearance occurred approximately twice as fast (approximately 5 min earlier) and early insulin exposure (AUCIAsp,0–30min) was approximately 1.5- to 2-fold greater for faster aspart versus insulin aspart. Likewise, onset of action occurred approximately 5 min faster and early glucose-lowering effect (AUCGIR,0–30min) was approximately 1.5- to 2-fold larger for faster aspart versus insulin aspart. Relative bioavailability was approximately 100% and total glucose-lowering effect was similar for faster aspart versus insulin aspart. Dose–concentration and dose–response relationships were comparable between faster aspart and insulin aspart. Within-subject variability in glucose-lowering effect was low for faster aspart (coefficient of variation approximately 20%) and not significantly different from insulin aspart.ConclusionThe faster onset and greater early insulin exposure and glucose-lowering effect with faster aspart versus insulin aspart are preserved across a broad range of doses and consistently observed from day to day.ClinicalTrials.gov identifierNCT02033239.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-016-0473-5) contains supplementary material, which is available to authorized users.