1. Key publication slides
Heinemann L, et al.
Pharmacokinetic and pharmacodynamic properties of a novel inhaled insulin.
Journal of Diabetes Science and Technology. 2017;11:
Key publication slides
No FXCX

2. Rationale for Developing Ultra-Fast-Acting Insulins
Fast-acting insulin analogues (e.g. insulin lispro) have improved PK/PD properties compared with regular human insulin1
However, s.c. administration slows insulin absorption, resulting in delayed onset of action and prolonged duration of action compared with endogenous insulin activity in healthy individuals2,3
Delayed onset of action/prolonged duration of action can lead to:
Suboptimal control of early postprandial hyperglycaemia
Risk of late-postprandial hypoglycaemia
Ultra-fast-acting insulin analogues with a more rapid onset of action and shorter duration of action are needed
1. Heinemann L, et al. Diabet Med. 1996;13: Chen JW, et al. Diabetes Obes Metab. 2003;5: Home PD. Diabetes Obes Metab. 2015;17:
PD, pharmacodynamic; PK, pharmacokinetic; s.c., subcutaneous.

3. Technosphere® Inhaled Insulin (TII): An Inhaled Insulin Delivery System
Property
Description
Formulation
Inhalation powder containing recombinant human insulin adsorbed onto FDKP microparticles
Microparticle size
2.0–2.5 μm (optimized for delivery to the deep lung)
Insulin absorption
Upon delivery to the deep lung, mircroparticles dissolve in the alveoli, allowing for rapid absorption of insulin into circulation
Excipient (FDKP)
Biologically inactive and excreted unchanged in urine
Inhaler
MedTone® inhaler
Required 2 inhalations per cartridge
Gen2® inhaler
Smaller, more efficient (less powder per dose)
Requires 1 inhalation per cartridge
Cartridges
Contain 10, 20, or 30 U (labelled as 4, 8, or 12 U, respectively)a
a Labels refer to equivalent dose for a patient transitioning from subcutaneously administered insulin). FDKP, fumaryl diketopiperazine; U, units.
Heinemann L, et al. J Diabetes Sci Technol. 2017;11:

4. Faster onset of appearance and faster clearance vs insulin lispro
PK Profile of TII
8 U TII
8 U Insulin lispro (s.c.) 10 20 30 40 50 60 70 80
Insulin (µU/mL)
-20 20 60
120
140
180
200
220
240
280
340
360 40
100
160
260
320
300 80
Time (minutes)
Faster onset of appearance and faster clearance vs insulin lispro
Reproduced from Heinemann L, et al. J Diabetes Sci Technol. 2017;11: © 2016 Diabetes Technology Society.

5. Baseline-corrected GIR (mg/kg/min)
PD Profile of TII
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
TII
Insulin lispro (s.c.)
Baseline-corrected GIR (mg/kg/min)
100
200
300
400
500
600
Time (minutes)
Rapid onset of action and shorter duration of action vs insulin lispro
Reproduced from Heinemann L, et al. J Diabetes Sci Technol. 2017;11: © 2016 Diabetes Technology Society.
GIR, glucose infusion rate.

6. Clinical Use of TII
Clinical data indicate that TII may reduce postprandial hyperglycaemia (including late-postprandial hypoglycaemia) compared with fast-acting insulin analogues1-3
Addition of TII to a closed-loop artificial pancreas system also improves postprandial glycaemic control without increasing the risk of hypoglycaemia4
Switching patients from s.c. insulin to TII
Cartridges containing 10, 20, or 30 U (labelled as 4, 8, or 12 U) are used to replace s.c. doses of 4, 8, or 12 U, respectively
Potency of inhaled insulin is less than s.c. equivalent, so dose titration is expected1
Adjustment of basal insulin dose may be necessary1
Due to its short duration of action, a second dose may be required 1.5–2 hours after first inhalation to manage extended postprandial hyperglycaemia2
1. Bode BW, et al. Diabetes Care. 2015;38:
2. Rosenstock J, et al. Lancet. 2010;375:
3. Kapsner P, et al. Diabeteologia. 2009;52 Suppl1:S386 [abstract 982].
4. Zisser H, et al. J Diabetes Sci Technol. 2015;9:

7. Summary
TII has a more rapid absorption and clearance than s.c. fast-acting insulin analogues
These properties result in a faster onset of action and shorter duration of action
May provide better glycaemic control in the early postprandial phase
May reduce the risk of late-postprandial hypoglycaemia
Transitioning patients from s.c. insulin to TII
Dose titration of TII is expected
An increase in the basal insulin dose may be necessary
Due to its short duration of action, a second dose may be required 2 hours after the first to manage extended postprandial hyperglycaemia
Heinemann L, et al. J Diabetes Sci Technol. 2017;11: