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The ADA recommends patients spend ≥70% Time in Range (TIR) per day1
AFREZZA® ambulatory glucose profile case example2
Line graph highlighting an AFREZZA ambulatory glucose profile case example with a shaded region showing Time in Range.
Improved TIR correlates well with A1C1
CGM data from a single AFREZZA patient.2
AFREZZA added to existing treatments significantly improved Time in Range3
Bar chart showing how AFREZZA resulted in a 56% relative increase in Time in Range over 12 weeks.
Mean daily BG levels decreased by 41 mg/dL (P<0.0002), a 20% relative decrease3
change in tIR over 12 weeks3

Data from an open-label, non-randomized, clinical research study of 20 adult patients (≥18 years old) with T2D and inadequately controlled (A1C 7.5% to 11.5%) after at least 6 months of other diabetes treatments, including OAs and basal insulin. AFREZZA treatment was added to each patient’s current therapy, administered before each meal, and titrated per protocol. A1C and blinded CGM measurements were recorded at baseline and end of study, patients continued to self-monitor blood glucoses daily. CGM data were incomplete for 1 patient.3

AFREZZA increased Time in Range3,4
Bar chart showing how patients treated with AFREZZA gained roughly 2 hours in Time in Range each day.
Patients* gained ~2 hours in TIR each day4
TIR WITH AFREZZA VERSUS SC RAI4
Data from the STAT study of patients with T1D with A1C levels 6.5% to 10%. Individuals were randomized to treatment with titrated AFREZZA (n=22) or titrated SC RAI aspart (n=34) and included in the final analysis. All were required to wear a real-time CGM throughout the trial.4
*Patients were defined as compliant if ±90% of postmeal AFREZZA dosages were taken per protocol, with at least one of the postmeal inhalations taken if indicated per meal.4
Immediate and significant post-mealtime control4
Line graph showing how AFREZZA significantly improved post-mealtime control without increased time in hypoglycemia.
AFREZZA improved PPG without any increased time in hypoglycemia4
PPG LEVELS ASSOCIATED WITH AFREZZA VERSUS SC RAI4*
Data from the STAT study of patients with T1D with A1C levels 6.5% to 10%. Individuals were randomized to treatment with titrated AFREZZA (n=22) or titrated SC RAI aspart (n=34). All were required to wear a real-time CGM throughout the trial. Only data from AFREZZA-compliant patients is shown.4
*Patients were defined as compliant if ±90% of postmeal AFREZZA dosages were taken per protocol, with at least one of the postmeal inhalations taken if indicated per meal.4
Significantly lower PPG levels within 1-4 hours post-meal compared with SC RAI (P<0.05)4
  • At 60 minutes post-meal, patients in the AFREZZA group demonstrated significantly lower PPG levels compared with SC RAI, indicating a more rapid initial glucose control4
  • The effect persists at 90 minutes, with AFREZZA maintaining lower glucose levels with statistical significance4
  • By 120 minutes, the PPG levels with AFREZZA are still significantly lower compared with SC RAI, suggesting rapid action of the inhaled insulin more closely aligns to natural insulin activity post-meal4
Reduced risk and severity of hypoglycemia5
Bar chart showing how AFREZZA significantly lowered hypoglycemic events after the first 2 hours of dosing.
Hypoglycemic events were significantly lower after the first 2 hours of dosing5
HYPOGLYCEMIA EVENT RATE WITH AFREZZA VERSUS SC RAI5
Data from a post-hoc regression analysis on a subset of the AFFINITY-1 study of adults (n=279) with T1D ≥12 months and an A1C level of 7.5% to 10%. Patients were randomized to receive basal insulin plus either AFREZZA or SC RAI aspart. These results should be interpreted along with the efficacy results for this study.5
  • The ultra-rapid time–action profile of AFREZZA may contribute to its reduced risk of hypoglycemic events compared with SC RAIs5
Bar chart showing how AFREZZA delivered a lower rate of severe hypoglycemia versus subcutaneous RAI.
Results align with full AFFINITY-1 safety analysis5,6
LOWER RATE OF SEVERE HYPOGLYCEMIA WITH AFREZZA VERSUS SC RAI5
Data from a post-hoc regression analysis on a subset of the AFFINITY-1 study of adults (n=279) with T1D ≥12 months and an A1C level of 7.5% to 10%. Patients were randomized to receive basal insulin plus either AFREZZA or SC RAI aspart. A 5% significance level was used throughout the study. These results should be interpreted along with the efficacy results for this study.5
AFREZZA effectively lowers A1C3,6
In the AFFINITY-1 pivotal T1D trial, patients treated with AFREZZA and patients treated with SC RAI achieved similar average A1C reductions from baseline. Baseline A1C levels were 7.94% for patients treated with AFREZZA and 7.92% for patients using SC RAI. By week 24, AFREZZA reduced A1C to 7.73% (-0.21%), and SC RAI to 7.52% (-0.40%), resulting in a between-group difference of 0.19%6
MEAN A1C LEVELS OVER 24-WEEK TREATMENT PERIOD6
Data from an open-label, non-inferiority trial compared the change in A1C from baseline to Week 24 of prandial AFREZZA (n=174) with that of SC RAI (n=170), both with basal insulin, in adult patients (≥18 years) with T1D and A1C of 7.5% to 10%. AFREZZA provided less A1C reduction than RAI, satisfied the non-inferiority margin of 0.4%, and the difference was statistically significant. More subjects in the SC RAI group achieved the A1C target of ≤7%.6
AFREZZA significantly decreased A1C levels in uncontrolled patients3
Downward arrow indicating an average A1C reduction of 1.6% with AFREZZA.
Average A1C reduction was 1.6%
Mean baseline A1C 9.0% reduced to 7.4% in patients with T2D (P<0.0001)3
MEAN CHANGE IN A1C LEVELS OVER TREATMENT COURSE3
Data from an open-label, non-randomized, clinical research study of 20 adult patients (≥18 years old) with T2D and inadequately controlled (A1C 7.5% to 11.5%) after at least 6 months of other diabetes treatments, including OAs and basal insulin. AFREZZA treatment was added to each patient’s current therapy, administered before each meal, and titrated per protocol. A1C and blinded CGM measurements were recorded at baseline and end of study, patients continued to self-monitor blood glucoses daily.3
Across clinical trials, AFREZZA was associated with a neutral weight profile4,6-10
Cross-trial comparison should not be made due to differences in patient populations and trial designs.
*Values represent the sample size at the end of the respective studies

A1C=glycated hemoglobin; BG=blood glucose; CGM=continuous glucose monitor; IQR=interquartile range; OAs=oral antidiabetic agents; PPG=postprandial glucose; PPGE=postprandial glucose excursions; SC RAI=subcutaneous rapid-acting insulin; T1D=type 1 diabetes; T2D=type 2 diabetes; TIR=time in range.

References: 1. American Diabetes Association Professional Practice Committee. 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes—2024. Diabetes Care. 2924;47(Supplement_1):S111-S125. 2. Data on file. MannKind Corporation. 3. Levin P, Hoogwerf BJ, Snell-Bergeon J, Vigers T, Pyle L, Bromberger L. Ultra rapid-acting inhaled insulin improves glucose control in patients with type 2 diabetes mellitus. Endocr Pract. 2021;27(5):449-454 4. Akturk HK, Snell-Bergeon JK, Rewers A, et al. Improved postprandial glucose with inhaled Technosphere insulin compared with insulin aspart in patients with type 1 diabetes on multiple daily injections: the STAT study. Diabetes Technol Ther. 2018;20(10):639-647. 5. Seaquist ER, Blonde L, McGill JB, et al. Hypoglycaemia is reduced with use of inhaled Technosphere® Insulin relative to insulin aspart in type 1 diabetes mellitus. Diabet Med. 2020;37(5):752-759. 6. Bode BW, McGill JB, Lorber DL, Gross JL, Chang PC, Bregman DB. Inhaled Technosphere insulin compared with injected prandial insulin in type 1 diabetes: a randomized 24-week trial. Diabetes Care. 2015;38(12):2266-2273. 7. McGill JB, Peters A, Buse JB, et al. Comprehensive Pulmonary Safety Review of Inhaled Technosphere® Insulin in Patients with Diabetes Mellitus. Clin Drug Investig. 2020;40(10):973-983. 8. Hoogwerf BJ, Pantalone KM, Basina M, et al. Results of a 24-week trial of technosphere insulin versus insulin aspart in type 2 diabetes. Endocr Pract. 2021;27(1):38-43. 9. Rosenstock J, Lorber DL, Gnudi L, et al. Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomised trial. Lancet. 2010;375(9733):2244-2253. 10. Rosenstock J, Franco D, Korpachev V, et al. Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents. Diabetes Care. 2015;38(12):2274-2281.

© MannKind Corporation June, 2024. US-AFR-2499

Indications and Usage

Afrezza® (insulin human) Inhalation Powder is a rapid acting inhaled human insulin indicated to improve glycemic control in adult patients with diabetes mellitus.

Limitations of Use: Not recommended for the treatment of diabetic ketoacidosis, not recommended in patients who smoke or have recently stopped smoking.

Important Safety Information for Afrezza® (insulin human) Inhalation Powder

WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE. Acute bronchospasm has been observed in patients with asthma and COPD using AFREZZA. AFREZZA is contraindicated in patients with chronic lung disease such as asthma or COPD. Before initiating AFREZZA, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.

Indications and Usage:

AFREZZA® (insulin human) Inhalation Powder is a rapid acting inhaled human insulin indicated to improve glycemic control in adult patients with diabetes mellitus.

Limitations of Use: Not recommended for the treatment of diabetic ketoacidosis, not recommended in patients who smoke or have recently stopped smoking.

Important Safety Information

WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE

  • Acute bronchospasm has been observed in AFREZZA-treated patients with asthma and COPD.
  • AFREZZA is contraindicated in patients with chronic lung disease such as asthma or COPD.
  • Before initiating AFREZZA, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.

Contraindications

AFREZZA is contraindicated: during episodes of hypoglycemia, in patients with chronic lung disease (such as asthma or chronic obstructive pulmonary disease [COPD]) because of the risk of acute bronchospasm, and in patients with hypersensitivity to regular human insulin or any of the excipients in AFREZZA.

Warnings and Precautions

Acute Bronchospasm: In a study of patients with asthma whose bronchodilators were temporarily withheld for assessment, bronchoconstriction and wheezing following AFREZZA dosing was reported. Before initiating therapy, evaluate all patients with a medical history, physical examination, and spirometry (FEV1) to identify potential underlying lung disease. Do not use in patients with chronic lung disease such as asthma or COPD.

Hypoglycemia or Hyperglycemia with Changes in Insulin Regimen: Glucose monitoring is essential for patients receiving insulin therapy. Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. These changes should be made under close medical supervision and the frequency of blood glucose monitoring should be increased. For patients with type 2 diabetes, dosage modifications of concomitant oral antidiabetic treatment may be needed.

Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulins, including AFREZZA. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly, and symptoms may differ across patients and change over time in the same patient. Patients and caregivers should be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia.

Decline in Pulmonary Function: AFREZZA causes a decline in lung pulmonary function over time as measured by FEV1. In clinical trials excluding patients with chronic lung disease and lasting up to 2 years, AFREZZA-treated patients experienced a small (40 mL) but greater FEV1 decline than comparator-treated patients. Assess pulmonary function with spirometry at baseline, after the first 6 months of therapy and annually thereafter even in the absence of pulmonary symptoms. In patients who have a decline of ≥20% in FEV1 from baseline, consider discontinuing AFREZZA. Consider more frequent lung function assessment in patients with pulmonary symptoms, e.g., wheezing, bronchospasm, breathing difficulties, or persistent or recurring cough. If symptoms persist, discontinue AFREZZA.

Lung Cancer: In clinical trials, 2 cases of lung cancer were observed in patients exposed to AFREZZA while no cases were reported for the comparators. In both cases, a prior history of heavy tobacco use was identified as a risk factor for lung cancer. Two additional cases of lung cancer (squamous cell and lung blastoma) were reported in non-smokers exposed to AFREZZA after the trial completion. These data are insufficient to determine whether AFREZZA has an effect on lung or respiratory tract tumors. In patients with active lung cancer, a prior history of lung cancer, or in patients at risk of lung cancer, consider whether the benefits of AFREZZA use outweigh this potential risk.

Diabetic Ketoacidosis (DKA): In clinical trials enrolling patients with type 1 diabetes, diabetic ketoacidosis (DKA) was more common in AFREZZA-treated patients (0.43%; n=13) than in comparator-treated patients (0.14%; n=3). Patients with type 1 diabetes should always use AFREZZA in combination with basal insulin. In patients at risk for DKA, such as those with an acute illness or infection, increase the frequency of glucose monitoring and consider discontinuing AFREZZA and giving insulin using an alternate route of administration.

Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including AFREZZA. If hypersensitivity reactions occur, discontinue AFREZZA, treat per standard of care and monitor until symptoms and signs resolve.

Hypokalemia: All insulin products, including AFREZZA, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Closely monitor potassium levels in patients at risk of hypokalemia and treat if indicated.

Fluid Retention and Heart Failure with Concomitant Use of Thiazolidinediones (TZDs): Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of TZDs and insulin. Observe these patients for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the TZD should be considered.

Drug Interactions

Certain drugs may affect glucose metabolism, increasing the risk of hypoglycemia, or decreasing or increasing the blood glucose lowering effect of AFREZZA. Dose adjustment and increased frequency of blood glucose monitoring may be required. Co-administration of beta-blockers, clonidine, guanethidine, and reserpine with AFREZZA may reduce the signs and symptoms of hypoglycemia. For full list, see Prescribing Information.

Adverse Reactions

The most common adverse reactions associated with AFREZZA are hypoglycemia, cough, and throat pain or irritation.

To report SUSPECTED ADVERSE REACTIONS, contact MannKind Corporation at 1-877-323-8505 or FDA at www.fda.gov/medwatch or call 1-800-FDA-1088 (1-800-332-1088).

Please see full Prescribing Information, including BOXED WARNING for AFREZZA.