1. Inhaled Human Insulin and its Place in Therapy
Breanne Fleming, PharmD
PGY2 Ambulatory Care Resident
Richard L. Roudebush VA Medical Center
This speaker has no actual or potential conflicts of interest to disclose in relation to this presentation

2. Exubera® Inhaled Human Insulin
Introduced in mid 2006-
1 or 3 mg blisters; 3 mg = 8 units
Similar onset
Similar CI and precautions
Mack GS. Nat Biotechnol Dec;25(12):

3. Exubera® Inhaled Human Insulin
Challenges
Size of device
Difficult dose adjustment
Dosage form inconsistencies
Risk of lung disease
Insurance barriers
Withdrawn from the market in 2007
Issues with insurance companies covering because it was not BETTER than subQ but cost 30% more
Removed from the market in 2007 d/t lack of consumer interest.
Other drug companies stopped development of their own inhaled insulin products – with the exception of the makers of Afrezza
Mack GS. Nat Biotechnol Dec;25(12):
Business Week. Pfizer’s Exubera Flop. Available at: Accessed July 25, 2014.

4. Afrezza® Inhaled Human Insulin
FDA approved June 2014
Patients with type 1 and type 2 diabetes
Ultra rapid-acting insulin
Not yet available
Similar onset
Similar CI and precautions
Smaller and more convenient design
Single-use cartridges, powdered regular insulin – inhaler is used to aerosolize that powder for absorption.
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

5. Afrezza® Inhaled Human Insulin
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

6. Steps for Use Open device and snap in cartridge
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

7. Steps for Use
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

8. Steps for Use Single use cartridge, discard when done
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

9. Afrezza® Inhaled Human Insulin
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

10. Storage Store in refrigerator
Inhaler good for 15 days from date of first use – then discard and replace with new inhaler
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

11. Initiating Inhaled Insulin
Insulin naïve
Start 4 units at each meal
Patients on subcutaneous mealtime insulin
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

12. Adverse Reactions Hypoglycemia Cough Throat pain/irritation
Acute bronchospasm in patients with chronic lung disease
Decline in pulmonary function
Lung cancer
Diabetic ketoacidosis (DKA)
Hypersensitivity reactions
REMS for bronchospasm
Check pulmonary function even if no symptoms – consider d/c if pt experiences >20% decline in FEV1 from baseline
Pulmonary function Spirometry at baseline, 6 months, then annually
resolved with discontinuation of inhaled insulin
4 cases of lung cancer so far, same risk with Exubera
Patients at increased risk for DKA
More patients experienced DKA vs. subcutaneous insulin (0.43% vs. 0.14%) very small sample size
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

13. Contraindications Patients with chronic lung disease
Asthma
COPD
History of hypersensitivity to regular human insulin or any excipients
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

14. Pharmacokinetics Clinical Effect Absorption
A = onset of activity no difference vs. lispro
B = max serum concentrations
Regular insulin hours duration 8 hours
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014. .

15. *OAD= max dose metformin or >2 oral antidiabetic agents
Clinical Evidence
Population:
Patients with T2DM
Intervention:
Inhaled insulin + OAD*
vs.
placebo + OAD*
*OAD= max dose metformin or >2 oral antidiabetic agents
Primary Outcome:
Reduction in HgbA1c
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

16. Clinical Evidence: Type 2 Diabetes
Efficacy Parameter
Afrezza + OAD
N= 177
Placebo + OAD
N= 176
Confidence Interval
Change in HgbA1c (%)
-0.82
-0.42
(-0.57, -0.23)
% Patients achieving HgbA1c < 7%
32.2
15.3 -
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

17. Clinical Evidence Population: Patients with T1DM Intervention:
Inhaled insulin + basal insulin vs.
aspart + basal insulin
344 patients more patients achieved HgbA1c<7 in aspart group
Aspart superior A1c reduction
Afrezza non-inferior
Primary Outcome:
Non-inferiority in HgbA1c reduction
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

18. Inhaled insulin + basal insulin
Clinical Evidence
Efficacy Parameter
Inhaled insulin + basal insulin
n = 174
Insulin aspart +
basal insulin
n = 170
Confidence Interval
Change in HgbA1c (%)
-0.21
-0.4
(-0.57, -0.23)
% Patients achieving HgbA1c < 7%
13.8
27.1 -
Afrezza(R) [package insert]. Danbury, CT: MannKind Corporation; 2014.

19. Patients who may benefit
Fear of needles
Dexterity issues
Post-meal hypoglycemia
Less weight gain
Severe hypoglycemia 43% lower than aspart in 1 study
Rosenstock J, et al. Lancet Jun 26;375(9733):

20. Inhaled Human Insulin and its Place in Therapy
Breanne Fleming, PharmD
PGY2 Ambulatory Care Resident
Richard L. Roudebush VA Medical Center