1. Key publication slides
Heise T, et al.
Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart.
Diabetes, Obesity and Metabolism. 2015;17:682-8.
Key publication slides
No FXCX

2. Background and Objectives
Fast-acting insulin analogues (e.g. insulin lispro, IAsp) provide a more physiological insulin profile than regular human insulin, and represent an important advance in the treatment of diabetes1,2
However, current fast-acting insulin analogues are still absorbed too slowly and do not mimic physiological insulin activity seen in healthy individuals3,4
Ultra-fast-acting IAsp is a new formulation of IAsp designed to accelerate absorption, thereby improving postprandial glycaemic control5
The aim of this study was to compare the PK/PD properties of ultra-fast-acting IAsp and IAsp in patients with T1D5
1. Brunner GA, et al. Diabet Med. 2000;17:371-5.
2. Heinemann L, et al. Diabet Med. 1996;13:625-9.
3. Heinemann L, Muchmore DB. J Diabetes Sci Technol. 2012;6:
4. Home PD. Diabetes Obes Metab. 2015;17:
5. Heise T, et al. Diabetes Obes Metab. 2015;17:682-8.
IAsp, insulin aspart; PD, pharmacodynamic; PK, pharmacokinetic; T1D, type 1 diabetes.

3. Study Design
Randomized, double-blind, single-dose, crossover, phase 1 trial (N = 52a)
Patients with T1D
Age 18–64 years
HbA1c ≤ 8.5%
BMI 18–28 kg/m2
Treated with MDI or CSII for ≥ 12 months
Ultra-fast-acting IAsp single dose (0.2 U/kg)
IAsp single dose(0.2 U/kg)
IAsp single dose (0.2 U/kg)
Ultra-fast-acting IAsp single dose (0.2 U/kg)
a 1 patient withdrew consent after 1 dose. BMI, body mass index; CSII, continuous subcutaneous insulin infusion; HbA1c, glycated haemoglobin A1c; MDI, multiple daily injections; U, units.
Heise T, et al. Diabetes Obes Metab. 2015;17:682-8.

4. Ultra-fast-acting IAsp (n = 51)
Results: Early Onset of Insulin Exposure With Ultra-Fast-Acting IAsp vs IAsp
Onset of insulin exposure, minutes
Ultra-fast-acting IAsp (n = 51)
IAsp (n = 51)
Treatment ratio [95% CI]
Onset of appearance
4.9
11.2
0.43 [0.36; 0.51]
t50%Cmax
20.7
31.6
0.65 [0.59; 0.72]
Faster onset of appearance with ultra-fast-acting IAsp
Earlier t50%Cmax with ultra-fast-acting IAsp
CI, confidence interval; t50%Cmax, time to reach 50% maximum concentration.
Heise T, et al. Diabetes Obes Metab. 2015;17:682-8.

5. Results: Greater Early Exposure With Ultra-Fast-Acting IAsp vs IAsp
1.3-fold increase in insulin AUC [95% CI 1.15; 1.43]
2.1-fold increase in insulin AUC [95% CI 1.76; 2.38]
4.5-fold increase in insulin AUC [95% CI 3.62; 5.66]
AUC0–15 minutes
AUC0–30 minutes
AUC0–1 hour
AUC0–1.5 hours
AUC, area under the curve.
Heise T, et al. Diabetes Obes Metab. 2015;17:682-8.

6. Ultra-fast-acting IAsp (n = 51)
Results: Early Onset of Glucose-Lowering Effect With Ultra-Fast-Acting IAsp vs IAsp
Onset of glucose-lowering effect, minutes
Ultra-fast-acting IAsp (n = 51)
IAsp (n = 51)
Treatment ratio [95% CI]
t50%GIRmax
38.3
46.1
0.83 [0.73; 0.94]
tGIRmax
124.3
135.2
0.92 [0.84; 1.01]
Faster t50%GIRmax with faster-acting Iasp
Similar tGIRmax
t50%GIRmax, time to reach 50% maximum glucose infusion rate; tGIRmax, time to reach maximum glucose infusion rate.
Heise T, et al. Diabetes Obes Metab. 2015;17:682-8.

7. Results: Greater Early Glucose-Lowering Effect With Ultra-Fast-Acting IAsp vs IAsp
1.2-fold increase in insulin AUC [95% CI 1.05; 1.30]
1.3-fold increase in insulin AUC [95% CI 1.18; 1.46]
1.5-fold increase in insulin AUC [95% CI 1.13; 2.02]
AUCGIR, 0–30 minutes
AUCGIR, 0–1 hour
AUCGIR, 0–1.5 hour
AUCGIR, 0–2 hours
GIR, glucose infusion rate.
Heise T, et al. Diabetes Obes Metab. 2015;17:682-8.

8. Conclusions
The new ultra-fast-acting formulation of IAsp has a more favourable PK/PD profile than IAsp
In the first 30 minutes following exposure, ultra-fast-acting IAsp is characterized by a:
57% earlier onset of appearance (4.9 minutes for ultra-fast-acting vs 11.2 minutes for IAsp)
2.1-fold increase in insulin exposure
1.5-fold increase in glucose-lowering effect
Total insulin exposure and glucose-lowering effects were similar for ultra-fast-acting IAsp and IAsp
These data suggest that ultra-fast-acting IAsp provides a more physiological insulin profile that may improve postprandial glycaemic control in patients with diabetes
Heise T, et al. Diabetes Obes Metab. 2015;17:682-8.