1. Key publication slides
Bode BW, et al.
Improved postprandial glycemic control with faster-acting insulin aspart in patients with type 1 diabetes using continuous subcutaneous insulin infusion.
Diabetes Technology and Therapeutics. 2017;19:25-33.
Key publication slides
No FXCX

2. Background and Objectives
For patients with T1D, CSII (also known as insulin pump therapy) is associated with improved glycaemic control compared with multiple daily injections1
However, excessive PPG excursions remain an issue with CSII,2 underscoring the need for a mealtime insulin with faster onset of action
Ultra-fast-acting IAsp is a new formulation of IAsp designed to accelerate insulin absorption3,4
When delivered by CSII, ultra-fast-acting IAsp increases early insulin exposure and glucose-lowering effect compared with IAsp in patients with T1D4
Total glucose-lowering effect is similar for ultra-fast-acting IAsp and IAsp4
The aim of this study was to compare ultra-fast-acting IAsp and IAsp in patients with T1D
Both were delivered by CSII
Comparison was based on 2-hour PPG response following a standardized meal test5
1. Misso ML, et al. Cochrane Database Syst Rev. 2010;1:CD James ML, et al. J Diabetes Sci Technol. 2016;10: Heise T, et al. Diabetes Obes Metab. 2015;17: Heise T, et al. Diabetes Obes Metab. 2017;19: Bode BW, et al. Diabetes Technol Ther. 2017;19:25-33.
CSII, continuous subcutaneous insulin infusion; IAsp, insulin aspart; PPG, postprandial glucose; T1D, type 1 diabetes.

3. Study Design: Randomized, double-blind, crossover trial
43 patients received faster IAsp or IAsp via CSII for 2 weeks
Primary endpoint: mean change in PPG 2 hours after a standardized meal test
Patients with T1D
Aged ≥ 18 years
HbA1c ≤ 9.0%
BMI ≤ 35 kg/m2
Treated with CSII for ≥ 3 months
Faster IAsp (via CSII for 2 weeks)
IAsp (via CSII for 2 weeks)
IAsp (via CSII for 2 weeks)
Faster IAsp (via CSII for 2 weeks)
BMI, body-mass index; HbA1c, glycated haemoglobin A1c.
Bode BW, et al. Diabetes Technol Ther. 2017;19:25-33.

4. Results: PPG Profiles With Ultra-Fast-Acting IAsp vs IAsp in CSII
Baseline-adjusted PG
−20 20 40 60 80
100
120
140 3 6 9 12 15 −1 1 2 3 4 5 6 7 50
100
150
200
250
PG (mmol/L)
Baseline-adjusted PG (mmol/L)
PG (mg/dL)
Baseline-adjusted PG (mg/dL)
IAsp Ultra-fast-acting IAsp
IAsp Ultra-fast-acting IAsp 30 60 90
120
150
180
210
240
−60
−30 30 60 90
120
150
180
210
Nominal time (minutes)
Nominal time (minutes)
Reproduced from Bode BW, et al. Diabetes Technol Ther. 2017;19: © Bruce W. Bode, et al., 2017; Published by Mary Ann Liebert, Inc.
PG, plasma glucose.

5. Results: Better Control of PPG With Ultra-Fast-Acting IAsp vs IAsp in CSII
Compared with IAsp, ultra-fast-acting IAsp provided a significantly greater glucose-lowering effect in the first hours following a standardized meal test
Mean change in PG was approximately 25% lower with ultra-fast-acting IAsp vs IAsp (3.03 mmol/L [54.68 mg/dL] vs mmol/L [75.52 mg/dL])a
ETD (95% CI): −0.99 mmol/L (−1.95; −0.03) [−17.84 mg/dL (−35.21; −0.46)]; p = 0.044
One hour post-meal PG level was mmol/L [29.47 mg/dL] lower with ultra-fast-acting IAsp than with IAsp (p = 0.006)
aData are least-squares means. ΔPGav, 0–2 hours, was calculated as AUCPG,0–2hours/2-hour PGPre-dose, where AUCPG,0–2 hours was the area under the PG concentration–time profile; mean change after 2 weeks. AUC, area under the curve; CI, confidence interval; ETD, estimated treatment difference.
Bode BW, et al. Diabetes Technol Ther. 2017;19:25-33.

6. Results: 2-Week Continuous Glucose Monitoring Data Confirm Earlier Onset of Action With Ultra-Fast-Acting IAsp vs IAsp
Early PPG excursion was lower with ultra-fast-acting IAsp vs IAsp after all meals, especially breakfast
Mean and peak postprandial IG levels (0–4 hours) were similar for ultra-fast-acting IAsp and IAsp after all meals
0.5
1.0
1.5
2.0
2.5
p = 0.004
p < 0.001
p = 0.015
p = 0.017
p = 0.523
p = 0.064
p = 0.320
Ultra-fast-acting IAsp IAsp 10 15 20 30 35 45 5 25 40
IG (mmol/L)
IG (mg/dL)
26:19
IG over 1 hour
IG over 1 hour
IG over 1 hour
IG over 1 hour
IG over 2 hours
IG over 2 hours
IG over 2 hours
IG over 2 hours
After all meals
After breakfast
After lunch
After dinner
Mean change (increment) in IG over 2 weeks of treatment.
Error bars represent standard error (mean).
IG, interstitial glucose.
Reproduced from Bode BW, et al. Diabetes Technol Ther. 2017;19: © Bruce W. Bode, et al., 2017; Published by Mary Ann Liebert, Inc.

7. Duration of low IG levels per 24 hours
Results: Less Time Spent in Hypoglycaemic State With Ultra-Fast-Acting IAsp vs IAsp
Ultra-fast-acting IAsp was associated with less time spent with low glucose level over a 24-hour period
≤ 3.9 mmol/L (70 mg/dL)
p = 0.557
p = 0.148
p = 0.039
p = 0.008
< 3.5 mmol/L (63 mg/dL)
< 3.0 mmol/L (54 mg/dL)
26:19
Ultra-fast-acting IAsp IAsp
< 2.5 mmol/L (45 mg/dL) 2 4 6 8 10 12 14 16 18 20 22 24
Duration of low IG levels per 24 hours
Reproduced from Bode BW, et al. Diabetes Technol Ther. 2017;19: © Bruce W. Bode, et al., 2017; Published by Mary Ann Liebert, Inc.
Error bars represent standard error (mean).

8. Conclusions
Compared with IAsp, PPG control was improved with ultra-fast-acting IAsp when used in a CSII setting in patients with T1D
Ultra-fast-acting IAsp was associated with:
Significantly smaller change in PPG in the first 2 hours following a standardized meal test
Significantly lower PPG level 1 hour after a standardized meal test
Improved PPG control after all meals, especially breakfast
Shorter duration of time spent in hypoglycaemic state over a 24-hour period
Bode BW, et al. Diabetes Technol Ther. 2017;19:25-33.