<h4>Background and objective</h4>Technosphere^® Insulin (TI), a human insulin powder for inhalation (Afrezza^®; MannKind Corporation, Westlake Village, CA, USA), is an ultra-rapid-acting inhaled insulin indicated to improve postprandial glycemic control in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Because TI is absorbed across the alveolar membrane, the objective of this analysis was to characterize its pulmonary safety.<h4>Methods</h4>Pooled data from 13 phase 2/3 clinical studies in 5505 patients with T1DM or T2DM treated with TI, Technosphere inhalation powder without insulin (TP; placebo), or active-comparator treatment were analyzed for incidences of respiratory treatment-emergent adverse events (TEAEs), changes in pulmonary function, and lung malignancies. Radiographic changes in the lungs were monitored in a subset of 229 patients.<h4>Results</h4>Among 3017 patients receiving TI, the median duration of TI exposure was 168 days; median active-comparator and TP exposure durations were 363 and 149 days for 2198 and 290 patients, respectively. Respiratory TEAEs were comparable across treatments, except for a higher incidence of mild cough with TI in active-comparator studies (28.0% vs. 5.2%). Slight reversible declines in pulmonary function from baseline were observed for TI versus TP and active-comparator treatments, including in a subpopulation of patients with retrospectively identified lung dysfunction. Lung malignancies were reported in two patients on active TI therapy with a smoking history. No clinically significant changes from baseline were observed in radiographic images.<h4>Conclusions</h4>Pulmonary safety assessment of the TI inhalation system did not identify any safety issues in individuals with either T1DM or T2DM.

d safety data from a clinical trial where in both type 1 (3017 patients) and type 2 (1991 patients) were studied which showed a reduction of HbA1c levels reduction by 0.4% in both groups at the end of 24 weeks. In another 24 week study involving 500 patients of type 1 DM, glycemic control was equal among Afrezza and injected rapidly acting insulin group, but the Afrezza group had less incidence of hypoglycemia probably due to rapid and short duration of action.[ 20 , 21 ] A 52-week randomized, open-label, parallel –group study evaluating the safety and efficacy of long-acting insulin + prandial TI (Technosphere Insulin) versus a twice daily injection of premixed insulin in patients of type 2 DM showed similar and non-inferior results.[ 16 , 17 , 20 ] It is not a substitute for long-acting insulin. It must be used in combination with long-acting insulin in patients with type 1 diabetes, and it is not recommended for the treatment of diabetic ketoacidosis (DKA) as trials suggest an increased incidence of DKA in patients on Afrezza. It is better not to be used in smokers as there is a possible risk of reduction in lung function.[ 17 , 20 ] ADVERSE EFFECTS The most common adverse reactions include hypoglycemia, cough, throat pain and irritation. There is some evidence reduction in FEV 1 of lung function, but overall long-term effects and the need for withdrawal has not yet been established as it is for its predecessor Exubera [ Figure 5 ]. Serious risk includes bronchospasm in patients with asthma, COPD and smokers.[ 17 , 20 , 21 , 22 ] Figure 5. Open in a new tab Insulin (Exubera) inhaler PRECAUTIONS AND CONTRAINDICATIONS Precaution should be taken in patients of asthma and COPD and in fluid retention and heart failure. It is contraindicated in hypoglycemia, hypersensitivity to regular human insulin, chronic lung disease such as asthma or COPD, active lung cancer and hypokalemia.[ 17 , 20 , 21 , 22 ] Pregnancy: Category C. INDICATIONS Type 1 and 2 DM: It should be used

Insulin therapy is a mainstay for treatment of diabetes mellitus; however, many barriers to insulin exist. Insulin human inhalation powder (technosphere insulin) is a new FDA-approved alternative to subcutaneous bolus insulin. This is an overview of technosphere insulin (TI). Pharmacokinetics, clinical efficacy, safety and tolerability are discussed. TI is more quickly absorbed than subcutaneous insulin therapies and has a shorter duration of action. It appears to be noninferior compared with subcutaneous insulin regimens, and is associated with less hypoglycemia. Thus, it may serve as an alternative insulin agent in patients reluctant to administer multiple subcutaneous injections of insulin daily or in patients who experience late postprandial hypoglycemia with subcutaneous insulin. Cough is the most common side effect, but tends to be mild and transient. A small decrease in the forced expiratory volume has been demonstrated, but does not appear to progress and is reversible. Patients should have periodic pulmonary function tests. TI is contraindicated in patients with chronic lung disease. The long-term risk of lung cancer is being monitored but at this point does not appear to be higher than the expected incidence of lung cancer in this population.

To review the pharmacology, pharmacokinetics, safety, and efficacy of Technosphere insulin (TI), a new inhaled insulin product. Searches were conducted in PubMed/MEDLINE, Scientific Citation Index, and abstracts from both the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) meetings from 2005 to August 2014, utilizing the search terms Afrezza, Technosphere, Afresa, and inhaled insulin. References were reviewed to identify additional sources. Studies with adequate sample sizes, evaluating clinically relevant end points were included. TI is approved by the Food and Drug Administration as a bolus insulin to treat patients with type 1 and type 2 diabetes. Its glucose-lowering properties are less than that of rapid-acting insulins, but it does demonstrate less hypoglycemia. TI's kinetics make it the fastest absorbed of any insulin available, although its overall onset of action appears similar to insulin lispro. It represents an alternative to bolus injections but would likely be used concomitantly with injected basal insulin. Major adverse effects are respiratory in nature, with cough being the most prominent. There is a small decrease in the forced expiratory volume in 1 s (FEV1) with TI; this appears to be consistent, nonprogressive, and reversible. Patients using TI must receive pulmonary function tests periodically throughout therapy. TI is contraindicated in patients with chronic lung disease and should be used with caution in patients who smoke. TI is a novel inhaled insulin that provides prandial coverage to patients with diabetes, representing an alternative to bolus insulin injections.

(November 2014). "Afrezza inhaled insulin: the fastest-acting FDA-approved insulin on the market has favorable properties". Journal of Diabetes Science As a medication, insulin is any pharmaceutical preparation of the protein hormone insulin that is used to treat high blood glucose. Such conditions include type 1 diabetes, type 2 diabetes, gestational diabetes, and complications of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic states. Insulin is also used along with glucose to treat hyperkalemia (high blood potassium level In… In 2006, the US Food and Drug Administration (FDA) approved the use of Exubera, the first inhalable insulin. It was withdrawn from the market by its maker in 2007 due to lack of acceptance. Inhaled insulin claimed to have similar efficacy to injected insulin, both in terms of controlling glucose levels and blood half-life. Currently, inhaled insulin is short-acting and is typically taken before meals; an injection of long-acting insulin at night is often still required. When people were switched from injected to inhaled insulin, no significant difference was observed in HbA1c levels over three months. Accurate dosing was a particular problem, although people showed no significant weight gain or pulmonary function decline over the length of the trial when compared to the baseline. Following its commercial launch in 2005 in the United Kingdom, it was not (as of July 2006) recommended by National Institute for Health and Clinical Excellence for routine use, except in cases where there is "proven injection phobia diagnosed by a psychiatrist or psychologist". In January 2008, the world's largest insulin manufacturer, Novo Nordisk, also announced that the company was discontinuing all further development of the company's own version of inhalable insulin, known as the AERx iDMS inhaled insulin system. Similarly, Eli Lilly and Company ended its efforts to develop its inhaled Air Insulin in March 2008. Afrezza, developed by Mannkind, was authorized by the FDA in June 2014 for use in adults with Type 1 and Type 2 diabetes, with a label restriction limiting its use only to those who also have asthma, active lung cancer, or chronic obstructive pulmonary disease (COPD). Rapid-acting inhaled insulin is a component of the drug-device combination solution that is used at the start of every meal. It employs technosphere technology, which appears to have a more practical delivery method and more dosing flexibility, and a new inhaled insulin formulation (2.5 m). A thumb-sized inhaler with improved dosage flexibility is used to deliver inhalable insulin. It includes powder-dissolved recombinant human insulin (fumaryl diketopiperazine). Technosphere insulin is quickly absorbed by…