Drug Update · Endocrinology

Insulin human (Afrezza): FDA Expands Indication to Ages ≥6

July 10, 2026

Label effective date

2026-05-30

Indication (exact)

Improve glycemic control in adult and pediatric patients 6 years of age and older with diabetes mellitus

T2DM primary result

HbA1c change -0.82 vs -0.42; difference -0.40 percentage points (95% CI -0.57 to -0.23) [NCT01451398] [12]

T1DM primary result

HbA1c change -0.21 vs -0.40; difference 0.19 percentage points (95% CI 0.02 to 0.36) [NCT01445951] [12]

Clinical Perspective

AFREZZA’s label expansion means endocrinologists, pediatric endocrinologists, primary care clinicians, and other prescribers treating diabetes now have an FDA-supported inhaled mealtime insulin indication that includes pediatric patients 6 years and older ^[1]^[3]. The revised label emphasizes baseline and periodic pulmonary assessment (spirometry FEV1) and contraindicates use in patients with chronic lung disease; the label also states AFREZZA is not recommended for patients who smoke or who have recently stopped smoking ^[1]^[3]. Prescribers should follow the recommended starting mealtime dosages and conversion guidance in the prescribing information and counsel patients on administration using the AFREZZA inhaler and cartridge system ^[1]^[3].

Dr. Amit Desai · Endocrinology

The FDA approved updated labeling for insulin human (AFREZZA®) expanding the indication to improve glycemic control in adult and pediatric patients 6 years of age and older with diabetes mellitus, effective May 29–30, 2026, with label revisions and prescribing information posted by FDA and DailyMed ^[3]^[1]. The approval references randomized trials in adults showing HbA1c effects versus comparator or placebo that are included in the full prescribing information ^[3].

Clinical Context

AFREZZA is a rapid-acting inhaled human insulin supplied as single-use inhalation cartridges for use with the AFREZZA inhaler; the product is manufactured and marketed by MannKind Corporation and is administered via oral inhalation ^[1]^[2]. The revised U.S. prescribing information and highlights state that AFREZZA is indicated to improve glycemic control in adult and pediatric patients 6 years and older with diabetes mellitus and is not recommended for diabetic ketoacidosis or in patients who smoke or have recently stopped smoking ^[1]^[3]. The label includes boxed warnings and contraindications related to acute bronchospasm in patients with chronic lung disease and directs baseline and periodic spirometry (FEV1) assessment ^[1]^[3].

Key Findings

In adults with type 2 diabetes mellitus, AFREZZA plus oral antidiabetic agents reduced HbA1c by 0.82 percentage points from an adjusted baseline of 8.25% versus a 0.42 percentage-point reduction with inhaled placebo (difference -0.40 percentage points; 95% CI -0.57 to -0.23) at 24 weeks in a randomized, double-blind, placebo-controlled study (NCT01451398) cited in the label ^[3].
In adults with type 1 diabetes mellitus in a 24-week, open-label, active-controlled study (NCT01445951), AFREZZA plus basal insulin reduced HbA1c by 0.21 percentage points from an adjusted baseline of 7.94% versus a 0.40 percentage-point reduction with insulin aspart plus basal insulin (difference 0.19 percentage points; 95% CI 0.02 to 0.36) at Week 24, meeting a pre-specified non-inferiority margin but showing a smaller HbA1c decrease versus insulin aspart in that trial ^[3].
The label notes AFREZZA has also been studied in pediatric patients aged 6 to 17 years with type 1 and type 2 diabetes mellitus; the prescribing information contains descriptions of pediatric clinical studies and safety assessments referenced in section 14 of the label ^[3].

Safety & Tolerability

The label includes a boxed warning: acute bronchospasm has been observed in AFREZZA-treated patients with asthma and COPD, and AFREZZA is contraindicated in patients with chronic lung disease such as asthma or COPD ^[1]^[3]. Prior to initiating AFREZZA, the label recommends a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease ^[1]^[3].
The most common adverse reactions reported with AFREZZA (≥2% incidence) are hypoglycemia, cough, and throat pain or irritation ^[1]^[2]^[3].
The prescribing information includes warnings about decline in pulmonary function (baseline spirometry, reassessment after 6 months and annually), potential considerations for lung cancer risk, diabetic ketoacidosis risk in at-risk patients, hypersensitivity reactions including anaphylaxis, hypokalemia, and fluid retention and heart failure when used with PPAR-gamma agonists ^[1]^[3].

Study Design

Key adult clinical trials described in the label include a 24-week, open-label, active-controlled study in adults with type 1 diabetes mellitus (NCT01445951) randomized after basal insulin optimization and a 24-week, double-blind, placebo-controlled study in adults with type 2 diabetes mellitus (NCT01451398) randomized after run-in; the type 2 trial randomized 353 patients to AFREZZA or inhaled placebo and the type 1 trial randomized 344 patients, with protocol-specified titration and maintenance periods and HbA1c as a primary outcome measure reported at Week 24 ^[3]. Details on pediatric trials and their design elements are provided in section 14 of the full prescribing information ^[3].

FAQ

Q1 What is AFREZZA (insulin human) approved for?

AFREZZA is approved to improve glycemic control in adult and pediatric patients 6 years of age and older with diabetes mellitus. The label specifies that AFREZZA is not recommended for the treatment of diabetic ketoacidosis and is not recommended in patients who smoke or who have recently stopped smoking. The approval and prescribing information revisions were effective in May 2026 and are reflected in the FDA label and DailyMed highlights. Clinicians should consult current prescribing information for complete dosing guidance.

Q2 How does AFREZZA work?

AFREZZA is a rapid-acting inhaled human insulin formulated as a dry powder for oral inhalation via the AFREZZA inhaler. As with other insulins, its mechanism is to lower blood glucose by stimulating peripheral glucose uptake and inhibiting hepatic glucose production; AFREZZA’s route of administration is inhalation using single-use cartridges with the AFREZZA Inhaler. The prescribing information describes pharmacology and clinical pharmacodynamics in section 12. Clinicians should consult current prescribing information for complete dosing guidance.

Q3 What is the recommended dose of AFREZZA?

The prescribing information provides recommended starting mealtime dosing and conversion tables: the initial dose in insulin‑naïve patients is 4 units inhaled at the beginning of each meal, and the label includes a conversion table for switching from other mealtime subcutaneous insulin regimens to AFREZZA (for example, up to 3 units → 4 units; 4–5 units → 8 units; 6–7 units → 12 units; 8 or more units → 16 units) and guidance on combining cartridges to achieve required mealtime dosages. The AFREZZA inhaler is used for oral inhalation with a single inhalation per cartridge, and the inhaler can be used for up to 15 days from first use. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of AFREZZA?

The most common adverse reactions reported with AFREZZA (incidence ≥2%) are hypoglycemia, cough, and throat pain or irritation. The label includes boxed warnings and contraindication for acute bronchospasm in patients with chronic lung disease, and recommends baseline and periodic spirometry (FEV1) assessments; AFREZZA is contraindicated in patients with asthma or COPD. Additional labeled warnings include decline in pulmonary function, potential considerations regarding lung cancer risk, diabetic ketoacidosis in at-risk patients, hypersensitivity including anaphylaxis, hypokalemia, and fluid retention/heart failure risk when used concomitantly with PPAR-gamma agonists. Clinicians should consult current prescribing information for complete dosing guidance.

Insulin human (Afrezza): FDA Expands Indication to Ages ≥6

Direct Clinical Takeaway & Evidence Summary

Insulin human (Afrezza): FDA Expands Indication to Ages ≥6

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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