What is the role of inhaled insulin, such as Afrezza (insulin human), in managing diabetes?

Inhaled Insulin in Diabetes Management

Inhaled insulin (Afrezza) serves as a rapid-acting prandial insulin option for adults with type 1 or type 2 diabetes who require mealtime insulin coverage, offering an alternative to injectable rapid-acting insulin analogs, but with significant pulmonary safety requirements and contraindications that limit its use. 1

Pharmacokinetic Profile and Clinical Role

• Inhaled insulin functions as an ultra-rapid-acting prandial insulin with faster pharmacokinetics than subcutaneous rapid-acting insulin analogs, making it suitable for mealtime glucose control 1, 2
• The medication peaks at approximately 40-60 minutes and has a duration of action of 2-3 hours, providing coverage for postprandial glucose excursions 3, 4
• Inhaled insulin must be used in combination with long-acting basal insulin in patients with type 1 diabetes and cannot serve as monotherapy 2, 5

Efficacy Compared to Injectable Insulin

• Clinical trials demonstrate that inhaled insulin is slightly less effective than subcutaneous insulin aspart, with mean HbA1c reductions of 0.21% versus 0.4%, respectively 3
• A pilot study suggests that supplemental doses of inhaled insulin based on postprandial glucose levels may improve blood glucose management without additional hypoglycemia or weight gain compared to injectable rapid-acting insulin, though larger confirmatory studies are needed 1
• Inhaled insulin is associated with lower rates of late postprandial hypoglycemia and less weight gain compared to subcutaneous rapid-acting insulin analogs 2, 3

Mandatory Safety Monitoring Requirements

All patients require spirometry (FEV1) testing to identify potential lung disease prior to and after starting inhaled insulin therapy 1

Absolute Contraindications

• Chronic lung disease including asthma and chronic obstructive pulmonary disease 1
• Active smoking or recent smoking cessation 1
• Diabetic ketoacidosis 2, 5
• Hypoglycemic episodes 5

Key Safety Concern

• Use of inhaled insulin may result in a decline in lung function (reduced FEV1) over time 1
• Cough is the most common adverse effect, reported by 24-33% of patients versus 2% with insulin aspart, typically occurring shortly after inhalation and usually mild 2, 3

Optimal Patient Selection

Consider inhaled insulin for patients who:

• Experience frequent late postprandial hypoglycemia with subcutaneous rapid-acting insulin 3
• Have needle phobia or significant psychological barriers to injectable insulin 3
• Develop skin reactions to subcutaneous insulin 3
• Are insulin-naive and hesitant to initiate traditional injectable insulin therapy 5

Do not use inhaled insulin in patients who:

• Have any chronic lung disease or respiratory symptoms 1
• Currently smoke or quit smoking recently 1
• Cannot comply with mandatory spirometry monitoring 1
• Require insulin for diabetic ketoacidosis treatment 2, 5

Practical Limitations

• The medication has a limited dosing range compared to injectable insulin options 1
• Frequent occurrence of cough limits tolerability in approximately one-quarter to one-third of patients 3
• Lack of long-term safety data regarding pulmonary effects restricts widespread adoption 3
• The requirement for periodic pulmonary function monitoring adds complexity to diabetes management 1, 3

Position in Treatment Algorithm

• Inhaled insulin represents an alternative prandial insulin option when advancing from basal insulin alone to combination injectable therapy, but is not preferred over subcutaneous rapid-acting insulin analogs due to slightly lower efficacy and pulmonary safety concerns 1
• When basal insulin has been titrated to acceptable fasting glucose levels but A1C remains above target, adding prandial insulin coverage is indicated—this can be accomplished with either injectable rapid-acting insulin analogs or inhaled insulin in carefully selected patients 1