Acute bronchospasm has been observed in patients with asthma and COPD using inhaled insulin. Use is contraindicated in patients with chronic lung disease such as asthma or COPD. Before initiating inhaled insulin, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.
Diabetes mellitus, types 1 and 2, treatment: Note: Insulin requirements vary dramatically between patients and therapy requires dosage adjustments with careful medical supervision. In patients with type 1 diabetes, inhaled insulin must be used concomitantly with intermediate- or long-acting (basal) insulin. In patients with type 2 diabetes, inhaled insulin is usually given in addition to a regimen that includes basal insulin and metformin, with or without other noninsulin agents (ADA 2021).
Initial dose:
Insulin-naive patients: Inhalation: 4 units at each meal.
Patients previously on SUBQ prandial insulin:
To replace the prandial insulin component with inhaled insulin, convert each SUBQ prandial dose to a prandial inhalation dose based on the following scale:
≤4 units SUBQ dose per meal: Inhalation: 4 units at each meal.
5 to 8 units SUBQ dose per meal: Inhalation: 8 units at each meal.
9 to 12 units SUBQ dose per meal: Inhalation: 12 units at each meal.
13 to 16 units SUBQ dose per meal: Inhalation: 16 units at each meal.
17 to 20 units SUBQ dose per meal: Inhalation: 20 units at each meal.
21 to 24 units SUBQ dose per meal: Inhalation: 24 units at each meal.
Patients previously on SUBQ premixed insulin:
To replace the basal insulin component, calculate the new daily basal insulin dose as half of the total daily injected premixed dose; administer as intermediate- or long-acting insulin SUBQ.
To replace the prandial insulin component with inhaled insulin, first estimate the SUBQ prandial dose by dividing half of the total daily SUBQ premixed insulin dose equally among 3 daily meals. Then, convert each estimated SUBQ prandial dose to a prandial inhalation dose based on the following scale:
Estimated ≤4 units SUBQ dose per meal: Inhalation: 4 units at each meal.
Estimated 5 to 8 units SUBQ dose per meal: Inhalation: 8 units at each meal.
Estimated 9 to 12 units SUBQ dose per meal: Inhalation: 12 units at each meal.
Estimated 13 to 16 units SUBQ dose per meal: Inhalation: 16 units at each meal.
Estimated 17 to 20 units SUBQ dose per meal: Inhalation: 20 units at each meal.
Estimated 21 to 24 units SUBQ dose per meal: Inhalation: 24 units at each meal.
Dosage adjustment: Adjust dosage in 4-unit increments if needed to achieve self-monitoring glucose targets and avoid hypoglycemia. Alternatively, may consider dosage adjustments based on the following recommendations for injectable prandial insulin in patients with type 2 diabetes:
To achieve self-monitoring glucose target: Adjust dose by 10% to 15% (ADA 2021).
For hypoglycemia: If no clear reason for hypoglycemia, decrease dose by 10% to 20%; for hypoglycemia requiring assistance from another person or blood glucose <40 mg/dL, reduce dose by 20% to 40% (AACE/ACE [Garber 2020]; ADA 2021).
Note: If glycemic targets are not achieved with increased inhaled insulin doses, consider the use of SUBQ prandial insulin.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no specific dosage adjustments provided in the manufacturer's labeling (has not been studied). Use with caution; increased glucose monitoring and dose reductions may be necessary.
There are no specific dosage adjustments provided in the manufacturer's labeling (has not been studied). Use with caution; increased glucose monitoring and dose reductions may be necessary.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder, Inhalation:
Afrezza: 4 units (90 ea); 8 units (90 ea); 12 units (90 ea); 4 units & 8 units (180 ea); 90 x 8 UNIT & 90x12 UNIT (180 ea); 4 units & 8 units & 12 units (180 ea) [contains polysorbate 80]
No
Afrezza combination packages containing a total of 90 cartridges are available as: 90 cartridges of 4 units, 30 cartridges of 4 units plus 60 cartridges of 8 units, 60 cartridges of 4 units plus 30 cartridges of 8 units, or 60 cartridges of 8 units plus 30 cartridges of 12 units.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022472s011lbl.pdf#page=12, must be dispensed with this medication.
For oral inhalation only. Administer at the beginning of the meal. Remove the amount/strength of cartridges needed for a single dose from packaging; multiple cartridges may be needed to achieve the correct dose. Allow cartridges to sit at room temperature for 10 minutes. Insert cartridge into the inhaler and snap to close. Keep inhaler level with mouthpiece on top and base on the bottom. Loss of drug may occur if inhaler is inverted, held with mouthpiece pointing down, shaken or dropped after cartridge is inserted but prior to dose administration. If any of these actions occur, a new cartridge must be loaded into the inhaler. Exhale fully. Close lips tightly around mouthpiece; do not exhale into inhaler. Tilt inhaler downward while keeping head level and inhale (rapidly, steadily and deeply). Hold breath for as long as comfortable at the same time removing the inhaler from the mouth. Exhale and continue to breathe normally. Throw away empty cartridge by removing it from the base; do not leave in inhaler. Repeat the steps for each cartridge needed for the correct total dose; use only one inhaler for multiple cartridges. Replace the inhaler every 15 days to maintain accurate drug delivery.
Diabetes mellitus, type 1 or type 2, treatment: Treatment of type 1 diabetes mellitus and type 2 diabetes mellitus to improve glycemic control.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error. Due to the number of insulin preparations, it is essential to identify/clarify the type of insulin to be used.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Endocrine & metabolic: Hypoglycemia (67%; severe hypoglycemia: 5%)
Respiratory: Cough (26%)
1% to 10%:
Gastrointestinal: Diarrhea (3%), nausea (2%)
Nervous system: Fatigue (2%)
Respiratory: Productive cough (2%), reduced forced expiratory volume (6%; ≥15% decline)
Frequency not defined:
Endocrine & metabolic: Weight gain
Immunologic: Antibody development (drug efficacy not affected)
Respiratory: Acute bronchospastic disease (patients with asthma)
Postmarketing: Respiratory: Bronchospasm
Hypersensitivity to regular insulin or any component of the formulation; during episodes of hypoglycemia; chronic lung disease such as asthma or COPD, due to risk of bronchospasm.
Documentation of allergenic cross-reactivity for insulin is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Diabetic ketoacidosis: In clinical trials involving type 1 diabetic patients, diabetic ketoacidosis (DKA) was observed more commonly with inhaled insulin than with comparators; increase glucose monitoring in patients at risk of DKA (eg, acute illness, infection) and if necessary, consider an alternative route of insulin administration. Inhaled insulin is not recommended for treatment of DKA.
• Hypersensitivity: Severe, life-threatening, generalized allergic reactions, including anaphylaxis, may occur. If hypersensitivity reactions occur, discontinue therapy, treat the patient with supportive care and monitor until signs and symptoms resolve.
• Hypoglycemia: The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from increased work or exercise without eating; use of long-acting insulin preparations (eg, insulin degludec, insulin detemir, insulin glargine) may delay recovery from hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.
• Hypokalemia: Insulin causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium in patients at risk for hypoglycemia.
• Lung cancer: Rare cases of cancer have been reported. In clinical trials, 2 cases were reported in patients with a history of heavy tobacco use; after clinical trial completion, 2 additional cases were reported in nonsmokers. The effect of inhalation powder on the development of lung or respiratory tract tumors is unknown. Use caution in patients with active lung cancer, a prior history of lung cancer, or in patients at risk for lung cancer.
• Pulmonary lung function decline: May cause a decline in lung function (measured by FEV1) over time; decline was observed within the first 3 months of therapy and persisted, but did not worsen, for therapy duration, up to 2 years. Assess PFTs at baseline, after the first 6 months of therapy and yearly thereafter, even in the absence of pulmonary symptoms. If FEV1 decline of ≥20% is observed, consider discontinuation. Frequently monitor patients with wheezing, persistent or recurring cough, bronchospasm, or breathing difficulties. If symptoms persist, discontinue the product.
Disease-related concerns:
• Bariatric surgery:
– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2020). Insulin secretion and sensitivity may be partially or completely restored after these procedures (Korner 2009; Peterli 2012). Rates and timing of type 2 diabetes improvement and resolution vary widely by patient. Insulin dose reduction of at least 75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014). Avoid the use of bolus insulin injections or dose conservatively with close clinical monitoring in the early phases after surgery.
– Weight gain: Insulin therapy is preferred if antidiabetic therapy is required during the perioperative period (Mechanick 2019). Evaluate risk versus benefit of long-term post-operative use and consider alternative therapy due to potential for insulin-induced weight gain (Apovian 2015).
• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.
• Chronic lung disease: [US Boxed Warning]: Acute bronchospasm has been observed in patients with asthma and chronic obstructive pulmonary disease (COPD) using inhaled insulin. Use is contraindicated in patients with chronic lung disease such as asthma or COPD. Before initiating inhaled insulin, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.
• Hepatic impairment: Use with caution in patients with hepatic impairment (has not been studied). Dosage requirements may be reduced and patients may require more frequent glucose monitoring.
• Renal impairment: Use with caution in patients with renal impairment (has not been studied). Dosage requirements may be reduced and patients may require more frequent glucose monitoring.
Special populations:
• Smokers: Use is not recommended in smokers or patients who have recently stopped smoking (safety and efficacy has not been established).
Other warnings/precautions:
• Appropriate use: Inhaled insulin is not a substitute for long-acting insulin and must be used in combination with long-acting insulin in patients with type 1 diabetes mellitus.
• Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Beta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Beta-Blockers (Nonselective): May enhance the hypoglycemic effect of Insulins. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Insulins. Risk C: Monitor therapy
Bortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapy
Etilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modification
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Liraglutide: May enhance the hypoglycemic effect of Insulins. Management: Consider reducing the liraglutide dose if coadministered with insulin. Prescribing information for the Saxenda brand of liraglutide recommends a dose decrease of 50%. Monitor blood glucose for hypoglycemia. Risk D: Consider therapy modification
Macimorelin: Insulins may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Metreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely for signs and symptoms of hypoglycemia. Risk D: Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Pioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, consider insulin dose reductions to avoid hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure, and consider pioglitazone dose reduction or discontinuation if heart failure occurs Risk D: Consider therapy modification
Pramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Risk D: Consider therapy modification
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Rosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Risk X: Avoid combination
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Information specific to the use of inhaled insulin during pregnancy is limited (Makam 2009).
Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2021; Blumer 2013).
Due to pregnancy-induced physiologic changes, insulin requirements tend to increase as pregnancy progresses, requiring frequent monitoring and dosage adjustments. Following delivery, insulin requirements decrease rapidly (ACOG 201 2018; ADA 2021).
Insulin is the preferred treatment of type 1 and type 2 diabetes mellitus in pregnancy, as well as gestational diabetes mellitus when pharmacologic therapy is needed. Agents other than inhaled insulin are currently preferred (ACOG 190 2018; ACOG 201 2018; Blumer 2013).
Refer to the Insulin Regular monograph for additional information related to the use of insulin in pregnancy.
Both exogenous and endogenous insulin are present in breast milk (study not conducted with this preparation) (Whitmore 2012). Insulin is not systemically absorbed via breast milk but may provide local benefits to the infant GI tract (Anderson 2018).
Appropriate glycemic control is required for the establishment of lactation in patients with diabetes mellitus (Anderson 2018). Breastfeeding provides metabolic benefits to mothers with type 1, type 2, and gestational diabetes mellitus as well as their infants; therefore, breastfeeding is encouraged (ACOG 201 2018; ADA 2021; Blumer 2013). Breastfeeding also influences maternal glucose tolerance; close monitoring of patients treated with insulin is recommended as dose adjustments may be required (ADA 2021; Anderson 2018). A small snack before breastfeeding may help decrease the risk of hypoglycemia in patients with pregestational diabetes (ACOG 201 2018; Reader 2004). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Plasma glucose (individualize frequency based on treatment regimen, hypoglycemia risk, and other patient-specific factors; some patients may be candidates for continuous glucose monitoring) (ADA 2021); electrolytes; renal function; hepatic function, weight; pulmonary function tests at baseline, after the first 6 months of therapy and yearly thereafter. Frequently monitor patients with wheezing, persistent or recurring cough, bronchospasm, or breathing difficulties.
HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2021; KDIGO 2020).
Recommendations for glycemic control in patients with diabetes:
Nonpregnant adults (ADA 2021):
HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.
Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).
Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).
Older adults (≥65 years of age) (ADA 2021):
Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).
HbA1c: <7% to 7.5% (healthy); <8% to 8.5% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.
Preprandial capillary blood glucose: 80 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).
Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).
Pregnant patients:
HbA1c: Pregestational diabetes (type 1 or type 2) (ADA 2021):
Preconception (patients planning for pregnancy): <6.5%.
During pregnancy: <6% (if can be achieved without significant hypoglycemia) or <7% if needed to prevent hypoglycemia.
Capillary blood glucose: Note: Less stringent targets may be appropriate if goals cannot be achieved without causing significant hypoglycemia (ADA 2021).
Gestational diabetes mellitus (ACOG 190 2018; ADA 2021):
Fasting: <95 mg/dL.
Postprandial: <140 mg/dL (at 1 hour) or <120 mg/dL (at 2 hours).
Pregestational diabetes mellitus (type 1 or type 2) (ADA 2021 ):
Fasting: 70 to 95 mg/dL.
Postprandial: 110 to 140 mg/dL (at 1 hour) or 100 to 120 mg/dL (at 2 hours).
Hospitalized adult patients (ADA 2020): Target glucose range: 140 to 180 mg/dL (majority of critically ill and noncritically ill patients; <140 mg/dL may be appropriate for selected patients, if it can be achieved without excessive hypoglycemia). Initiate insulin therapy for persistent hyperglycemia at ≥180 mg/dL.
Perioperative care in adult patients (ADA 2020): Target glucose range during perioperative period: Consider targeting 80 to 180 mg/dL.
Classification of hypoglycemia (ADA 2021):
Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.
Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.
Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.
Insulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Target organs for insulin include the liver, skeletal muscle, and adipose tissue.
Within the liver, insulin stimulates hepatic glycogen synthesis. Insulin promotes hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. Skeletal muscle effects of insulin include increased protein synthesis and increased glycogen synthesis. Insulin stimulates lipoprotein lipase synthesis and activity; this results in hydrolysis of triglycerides into free fatty acids and storage of free fatty acids in adipocytes, thereby reducing circulating triglyceride levels (Rawla 2018; Sadur 1982; Song 2019). In addition, insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.
Normally secreted by the pancreas, insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae. Inhaled human insulin has an identical structure to that of native human insulin and is adsorbed onto carrier particles which dissolve within the lungs after inhalation leading to rapid absorption of insulin in the systemic circulation. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Inhaled insulin is an ultra-rapid acting insulin.
Pharmacokinetic note: The carrier particles in the formulation are not metabolized and are eliminated unchanged in the urine following absorption in the lungs. Doses of 4, 12, and 48 units were studied in determining the pharmacokinetic profile.
Onset of action: ~12 minutes; Peak effect: ~35 to 55 minutes
Duration: ~90 to 270 minutes (proportional to dose)
Bioavailability: 21% to 30% compared with regular SubQ insulin (Nuffer 2015)
Half-life elimination: 120 to 206 minutes (apparent terminal half-life)
Time to peak, plasma: 10 to 20 minutes
Powder (Afrezza Inhalation)
4 unit (per each): $5.67
8 unit (per each): $11.35
12 unit (per each): $17.02
60x4 &60x8 &60x12 UNIT (per each): $11.35
90 x 4 UNIT &90x8 UNIT (per each): $8.51
90 x 8 UNIT &90x12 UNIT (per each): $14.18
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