When is an insulin inhaler, such as Afrezza (insulin human), recommended for adult patients with type 1 or type 2 diabetes, particularly those with stable diabetes and no history of chronic lung disease, such as chronic obstructive pulmonary disease (COPD) or asthma?

When to Use Inhaled Insulin

Inhaled insulin should be used as an alternative prandial (mealtime) insulin option for adults with type 1 or type 2 diabetes who need mealtime glucose coverage, but ONLY in carefully selected patients without chronic lung disease (asthma or COPD), who are non-smokers, and who have undergone baseline spirometry testing. 1

Primary Clinical Indications

For Prandial Coverage in Type 1 Diabetes

• Use inhaled insulin as an alternative to injectable rapid-acting insulin analogs for mealtime glucose control when combined with basal insulin. 1, 2
• It functions as ultra-rapid-acting prandial insulin with pharmacokinetics similar to rapid-acting analogs like lispro and aspart. 1, 2
• Must always be combined with long-acting basal insulin—inhaled insulin cannot replace basal insulin requirements. 3, 4

For Prandial Coverage in Type 2 Diabetes

• Consider when advancing from basal insulin alone to combination therapy and A1C remains above goal despite optimized basal insulin. 1, 2
• Use when basal insulin has been titrated to acceptable fasting glucose levels (or dose >0.5 units/kg/day) but A1C remains above target. 1, 2
• May be used as an alternative to adding injectable rapid-acting insulin or GLP-1 receptor agonists. 1, 2

Absolute Contraindications (Do Not Use)

Pulmonary Disease

• Chronic lung disease including asthma is an absolute contraindication. 1, 2
• Chronic obstructive pulmonary disease (COPD) is an absolute contraindication. 1, 2

Smoking Status

• Active smoking is an absolute contraindication. 1, 2
• Recent smoking cessation (within the past several months) is also a contraindication. 1, 2

Other Contraindications

• Not recommended for diabetic ketoacidosis treatment. 3

Mandatory Safety Requirements Before Initiation

Spirometry Testing Protocol

• All patients require baseline spirometry (FEV1) testing to identify potential lung disease BEFORE starting inhaled insulin. 1, 2
• Repeat spirometry testing is required after starting therapy for ongoing monitoring. 1, 2
• This requirement adds complexity to diabetes management and represents a significant practical limitation. 2

Expected Pulmonary Effects

• Use of inhaled insulin may result in decline in lung function (reduced FEV1). 1
• Most commonly reported adverse effect is mild cough occurring shortly after inhalation. 3, 5

Clinical Advantages Over Injectable Insulin

Pharmacokinetic Benefits

• Faster onset and shorter duration compared to injectable rapid-acting insulin analogs like lispro. 1
• Provides more physiologic prandial insulin coverage with rapid absorption. 3, 4

Metabolic Outcomes

• Achieves clinically meaningful A1C reductions comparable to injectable rapid-acting insulin. 1
• Associated with weight reductions compared to injectable insulin aspart over 24 weeks. 1
• Lower rates of hypoglycemia compared to injectable insulin products in clinical trials. 3

Patient Preference

• High patient satisfaction and preference over subcutaneous insulin injections. 5, 6
• May improve willingness to initiate insulin therapy in type 2 diabetes patients with injection aversion. 4, 5

Practical Limitations to Consider

Dosing Constraints

• Limited dosing range compared to injectable insulin options may restrict use in certain patients. 2
• Variable absorption in some patient populations. 7

Position in Treatment Algorithm

• Not preferred over subcutaneous rapid-acting insulin analogs due to slightly lower efficacy and pulmonary safety concerns. 2
• Represents a second-line alternative when patients refuse injectable prandial insulin. 2, 5

Common Clinical Pitfalls to Avoid

• Never use in patients with any history of chronic lung disease, even if well-controlled. 1, 2
• Never skip baseline spirometry testing—this is mandatory, not optional. 1, 2
• Do not use as monotherapy in type 1 diabetes—must combine with basal insulin. 3
• Do not assume it can replace basal insulin requirements in any patient. 4
• Remember to counsel patients about expected cough, which occurs in most patients but is typically mild. 3, 5