EFFICACY & SAFETY

Afrezza has been studied in over 3,000 patients with type 1 and type 2 diabetes1,2

Hand Inhaler

SWITCHING TO AFREZZA MAINTAINED ACCEPTABLE GLUCOSE CONTROL 9

Graph to show the mean A1C levels over a 24-week treatment periods.9

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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 rapid-acting insulin (n=170), both with basal insulin, in adult patients (≥18 years) with type 1 diabetes and A1C of 7.5% to 10%. Afrezza provided less A1C reduction than rapid-acting insulin, and the difference was statistically significant. More subjects in the SC rapid-acting group achieved the A1C target of ≤7%.9

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SWITCHING TO AFREZZA MAINTAINED ACCEPTABLE GLUCOSE CONTROL 9

ADDING AFREZZA SIGNIFICANTLY REDUCED A1C LEVELS COMPARED TO OAS ALONE10

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Study design: Double-blind, placebo controlled trial in patients with type 2 diabetes with an A1C ≥ 7.5% on metformin alone or 2 or more oral agents (OAs) randomized to receive prandial Afrezza (n=133) or prandial inhaled placebo (n=176).
The primary efficacy endpoint was the average change in A1C from baseline (randomization) to week 24. At week 24, Afrezza plus OAs had an A1C of -0.82%, OAs only had an A1C of -0.42% (P<0.0001).10

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ADDING AFREZZA SIGNIFICANTLY REDUCED A1C LEVELS COMPARED TO OAS ALONE10

WEIGHT PROFILE IN 2 PIVOTAL TRIALS9,10

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Study design (type 1): Open-label non-inferiority trial comparing the change in A1C baseline to week 24 of prandial Afrezza with SC rapid-acting insulin, both with basal insulin in adult patients with type 1 diabetes and an A1C >7.5%. Patients on Afrezza lost weight (-0.4 kg) compared with weight gain (+0.9) for patients on SC rapid-acting insulin (P=0.0102). Afrezza and basal insulin was therefore considered non-inferior to SC rapid-acting and basal insulin in terms of less weight gain.9

Study design (type 2): Double-blind placebo-controlled trial in patients with type 2 diabetes with an A1C ≥7.5% on metformin alone or 2 or more oral agents (OAs) randomized to receive prandial Afrezza (n=133) or prandial inhaled placebo (n=176). Over the 24-week treatment period, there was an average weight increase of 0.49 kg in the Afrezza group compared with a weight loss of 1.1 kg in the placebo group.10

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WEIGHT PROFILE IN 2 PIVOTAL TRIALS9,10

LET'S TALK ABOUT THE

SAFETY PROFILE

PATIENTS WITH TYPE 1 DIABETES1

The most common adverse reactions (excluding hypoglycemia) from pooled safety results in patients with type 1 diabetes.1

These adverse reactions were not present at baseline, occurred more commonly on Afrezza than on comparator, and occurred in at least 2% of patients treated with Afrezza.1

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PATIENTS WITH TYPE 1 DIABETES1

PATIENTS WITH TYPE 2 DIABETES1

The most common adverse reactions (excluding hypoglycemia) from pooled safety results in patients with type 2 diabetes.1

These adverse reactions were not present at baseline, occurred more commonly on Afrezza than on comparator, and occurred in at least 2% of patients treated with Afrezza.1

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PATIENTS WITH TYPE 2 DIABETES1

TOTAL HYPOGLYCEMIA AS A FUNCTION OF TIME IN THE TYPE 1 STUDY9

Study Design: This open-label non-inferiority trial compared the change in A1C from baseline to week 24 of prandial Afrezza (n = 174) with that of SC rapid-acting insulin (n = 170), both with basal insulin, in adult patients (≥ 18 years) with type 1 diabetes and A1C of 7.5% to 10%. 

Afrezza provided less A1C reduction than SC rapid-acting insulin, and the difference was statistically significant. More subjects in the SC rapid-acting insulin group achieved the A1C target of  7%.9

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TOTAL HYPOGLYCEMIA AS A FUNCTION OF TIME IN THE TYPE 1 STUDY9

COUGH

Graph to show incidence of cough in pooled safety population.1

Reported in 26.9% of Afrezza patients vs. 5.2% of comparator treated patients.1,2

94% of cough episodes were characterized as intermittent or single defined episodes.2

Cough was generally mild, dry, occurred within 10 minutes of inhalation, was transient and declined with continued use.2

In clinical trials, 2.8% of patients discontinued due to cough.1

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COUGH

LUNG FUNCTION TESTING

Monitoring lung function periodically is recommended with Afrezza.1

FEV1 is conducted to identify patients who experience a decline in lung function over time. Consider discontinuing Afrezza if patients experience a >20% decline in FEV1 from baseline.1

2% of patients experienced >20% decline in FEV1 from baseline in clinical trials.2

Diabetes is associated with an additional decline in FEV1 of 25 ml/year compared to healthy subjects.12 After age 25, FEV1 decreases at about 35-40 mL/year in healthy subjects.11


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LUNG FUNCTION TESTING
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Fev1 Callout

For more information on FEV1, please contact your Afrezza Territory Business Manager or click here.

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References

1. Afrezza (insulin human) Inhalation Powder Prescribing Information. MannKind Corporation.

2. Data on file. MannKind Corporation.

3. 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.

4. Peyrot M, Rubin RR, Kruger DF, et al. Correlates of insulin injection omission. Diabetes Care. 2010;33(2):240–245.

5. Lasalle JR, Berria R. Insulin therapy in type 2 diabetes mellitus: a practical approach for primary care physicians and other health care professionals. J Am Osteopath Assoc. 2013;113(3):152–162.

6. Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients. Diabetes Care. 2003;26(3):881-885.

7. Rave K, Heise T, Heinemann L, et al. Inhaled Technosphere insulin in comparison to subcutaneous regular human insulin: time action profile and variability in subjects with type 2 diabetes. J Diabetes Sci Technol. 2008;2(2):205–212.

8. Rossetti P, Porcellati F. Prevention of hypoglycemia while achieving good glycemic control in type 1 diabetes. Diabetes Care. 2008;31(2):S113–S120.

9. Bode BW, McGill JB, Lorber DL, et al. Inhaled Technosphere insulin compared with injected prandial insulin in type 1 diabetes: a randomized 24-week trial. Diabetes Care. 2015;38(12):2266–2273.

10. Rosenstock J, Franco D, Korpachev V, et al. Inhaled Technosphere insulin versus inhaled Technosphere placebo in insulin-naive subjects with type 2 diabetes inadequately controlled on oral antidiabetes agent. Diabetes Care. 2015;38(12):2274–2281.

11. Oldham PD. Decline of FEV1. Adapted from NHANES III equations. Thorax. 1987;42:161–164.

12. Lange P, Groth S, Mortensen J, et al. Diabetes mellitus and ventilatory capacity: a five year follow-up study. Eur Resp J. 1990;3(3):288–292.

13. Levin PA, Heinemann L, Boss A, et al. Impact of symptomatic upper respiratory tract infections on insulin absorption and action of Technosphere inhaled insulin. BMJ Open Diabetes Res Care. 2016;4:e000228.

14. 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.

Important Safety Information

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. 

Important Safety Information

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. 


Limitations of Use

  • AFREZZA is not a substitute for long-acting insulin. AFREZZA must be used in combination with long-acting insulin in patients with type 1 diabetes mellitus.
  • AFREZZA is not recommended for the treatment of diabetic ketoacidosis.
  • The safety and efficacy of AFREZZA in patients who smoke have not been established. The use of AFREZZA is not recommended in patients who smoke or who have recently stopped smoking (less than 6 months). 

Contraindications
AFREZZA is contraindicated in patients: 

  • During episodes of hypoglycemia
  • With chronic lung disease (such as asthma or chronic obstructive pulmonary disease [COPD]) because of the risk of acute bronchospasm
  • With hypersensitivity to regular human insulin or any of the AFREZZA excipients

Warnings and Precautions
Acute Bronchospasm: Before initiating therapy, evaluate patients with a medical history, physical examination and spirometry (FEV1) to identify potential underlying lung disease. Acute bronchospasm has been observed following AFREZZA dosing in patients with asthma and patients with COPD. The long-term safety and efficacy of AFREZZA in patients with chronic lung disease have not been established.


Changes in Insulin Regimen: Monitor blood glucose in all patients treated with insulin. Modify insulin regimen
and dose cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant oral antidiabetic treatment to help mitigate the risk of hypoglycemia or hyperglycemia.

Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin therapy, including AFREZZA, and may be serious and life-threatening. Educate patients and caregivers on mitigating the risks associated with hypoglycemia. Increased frequency of blood glucose monitoring is recommended for patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia.

Decline in Pulmonary Function: AFREZZA has been shown to cause a decrease in lung function as measured by FEV1. In clinical trials 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 initial 6 months of therapy and annually thereafter even in the absence of pulmonary symptoms. 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 reported 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 outweigh the risks.

Diabetic Ketoacidosis (DKA): Increase the frequency of glucose monitoring and consider an alternate route of administration of insulin in patients at risk for DKA.

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 if indicated.

Hypokalemia: 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 occurs, manage according to current standards and consider TZD dose reduction or discontinuation.

Adverse Reactions
The most common adverse reactions associated with AFREZZA (2% or greater incidence) are hypoglycemia, cough, and throat pain or irritation. 

Drug Interactions
Certain drugs may affect glucose metabolism, increasing the risk of hypoglycemia or decreasing 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, please see Full Prescribing Information.