Rohan S.*
Jeevan K. G.
Nikhil Ganesh S.
Mohammed Bilal
Burden Of Diabetes Mellitus
Diabetes mellitus is a progressive chronic metabolic disorder, characterised by continued elevated blood glucose caused by the secretion of insulin, the function of insulin, or both. However, because of the unpredictable nature of glucose, especially following a meal, the benefits of evolving pharmacology cannot be reflected in the attainment of good glycemic control for the vast majority of patients. In both T1DM and T2DM, maintaining tight glycemic control is essential in preventing both short-term and long-term complications.
Microvascular disease, including retinopathy, nephropathy, and neuropathy, as well as macrovascular disease, including cardiovascular disease and stroke, has all been attributed to poorly controlled diabetes. Due to the volatility of glucose, particularly after meals, even with the evolution of pharmacological therapy, the achievement of good glycemic control is not the reality for a significant portion of the patient population.(1)
Importance Of Postprandial Glucose (Ppg)
Plasma glucose concentration, 1 to 2 hours after the meal, is commonly termed postprandial glucose, or PPG. PPG contributes significantly to glycated haemoglobin (HbA1c) and is an important component of overall glycemic control, especially in the management of relatively well-controlled fasting blood glucose.
In healthy individuals, food intake elicits a rapid first-phase insulin response that suppresses hepatic glucose production and limits the increase of postprandial plasma glucose. In diabetic patients, the lack or the delay of this first-phase insulin release causes amplified postprandial plasma glucose excursions. Elevated PPG values have been correlated to endothelial dysfunction, oxidative stress, and high cardiovascular risk. As such, control of postprandial hyperglycemia is broadly accepted to be an important treatment goal, in addition to fasting blood glucose control.(2)
Limitations Of Subcutaneous Rapid-Acting Insulin
Insulin lispro, aspart and glulisine are examples of rapid-acting insulin analogues used frequently to control postprandial glycemia. They do not replicate true physiological insulin secretion, but are improved analogues compared with native human insulin in terms of pharmacokinetics.
Absorption is delayed by subcutaneous administration because insulin has to diffuse to the systemic circulation from the injection site. These agents are typically working within 15–30 min, peak in 1–2 hours and may work up to 4–6 hours. This delay means that the initial rise in postprandial glucose may not be fully controlled, whereas the prolonged working duration can increase the likelihood of late postprandial and nighttime hypoglycemia. Injections are also linked to pain, needle anxiety, and decreased adherence, particularly in patients who need several daily doses.(3)
Need For Alternative Insulin Delivery Systems
The search for alternative delivery methods that better mimic physiological insulin kinetics with improved patient convenience and compliance has risen in popularity in view of the limitations of subcutaneous insulin administration. Pulmonary drug delivery has become an attractive non-invasive alternative due to the vast surface area, rich vasculature, and thin epithelial barrier of the alveoli, which allow for rapid systemic absorption of agents such as insulin. The quick onset of action seen with inhaled insulin formulation also makes its action closely mimic that of postprandial hyperglycemia.
Furthermore, delivery of insulin through a non-needle delivery system can significantly improve patient acceptance, reduce injection-phobia, especially in patients who are reluctant to initiate injectable insulin therapy, and potentially lead to improved adherence. (4)
Introduction To Afrezza
Afrezza is a brand-new, fast-acting human insulin that may be breathed orally as a dry powder with the help of Technosphere® technology. Insulin particles have an extremely quick onset of effect because they are quickly absorbed into the circulation through the pulmonary epithelium upon inhalation.
Compared to subcutaneous rapid-acting insulins, Afrezza has a shorter duration of action and achieves peak plasma concentrations in around 12 to 15 minutes. This pharmacokinetic profile is especially useful in regulating early postprandial glucose spikes because it closely mimics the physiological first-phase insulin response.
Afrezza has the benefit of being a non-invasive, needle-free treatment in addition to its quick effect, which may increase satisfaction among patients and adherence. Yet there are certain restrictions on its usage, such as pulmonary safety issues and contraindications for people with persistent pulmonary conditions.(3)
Fig 1: Afrezza inhaler device and components. Created with BioRender.com based onpublicly available information.
PATHOPHYSIOLOGY AND COMPLICATIONS OF POSTPRANDIAL HYPERGLYCEMIA
Normal Insulin Response Vs Diabetic State
Glucose homeostasis is tightly controlled by coordinated insulin responses postprandially in non-diabetic subjects. Hyperglycaemia occurs postprandially and triggers rapid, biphasic secretion of insulin from the pancreatic cells. The initial phase of this process, which lasts only a few minutes, is designed to reduce the rise in blood glucose by inhibiting hepatic glucose synthesis; the later phases of this reaction are intended to make it easier for peripheral tissues (muscle and adipose) to absorb glucose from the circulation. Patients with diabetes, especially those with type 2 diabetes, on the other hand, are resistant to the effects of insulin and produce less of it. Lack, or attenuation, of early insulin secretion results in diminished uptake of glucose by peripheral tissues and increased production of glucose by the liver. This significantly contributes to total hyperglycaemia and produces profound late postprandial spikes.(5)
Consequences Of Postprandial Glucose Spikes (Cardiovascular Risk And Complications)
The effect of postprandial hyperglycemia in micro- and macrovascular disease complications associated with diabetes is becoming increasingly acknowledged. Beyond only raising the average glucose level, repeated postprandial variations in blood glucose lead to metabolic problems. Short-term rises in blood glucose stimulate enhanced generation of reactive oxygen species (ROS), leading to an oxidative stress that lies at the heart of the vascular damage.
On the endothelial level, the disturbance of endothelial availability of nitric oxide caused by postprandial glucose increases will trigger endothelial dysfunction, a crucial early event in the development of atherosclerosis. Moreover, spikes in blood glucose contribute to exacerbation of inflammation, induction of endothelial adhesion molecules and amplification of platelet activation, which all mediate vascular damage and atherosclerotic plaque formation.
In epidemiological and clinical trials, postprandial hyperglycemia has been identified as an independent marker for the occurrence of cardiovascular disease, even in patients with satisfactory control of fasting glucose levels, increasing the risk for stroke, myocardial infarction and total mortality, while consistent postprandial elevations of blood glucose levels predict progression of microvascular complications like nephropathy and retinopathy.
Hence, tackling postprandial glucose elevations should not only lead to optimal glucose control but also to lowering the long-term incidence of complications due to diabetes.(6)
OVERVIEW OF AFREZZA (TECHNOSPHERE INSULIN)
Composition, Formulation And Mechanism Of Pulmonary Absorption
Afrezza is an ultra-rapid-acting dry powder inhaled formulation of recombinant human insulin, developed and manufactured by MannKind with their technosphere technology. This comprises insulin, which has been adsorbed onto the fumaryl diketopiperazine (FDKP) carrier excipient, as microparticles of inert drug-carrier 2-3 µm in size, which is the range of particles that deposit in the alveoli (7). FDKP will self-assemble at acidic pH to form porous microparticles, onto which insulin is loaded at a predetermined, usually fixed, ratio, forming an insulin-carrier dry powder which can be inhaled(8). When the Technosphere particle is inhaled into the alveoli, it breaks down at physiological pH to release insulin and carrier. The quick absorption that follows produces an ultra-rapid pharmacodynamic profile that mimics early-phase, natural insulin release(9). The overall formulation is the drug-carrier system, comprising the drug: recombinant human insulin, and the drug-carrier: fumaryl diketopiperazine as the main excipient, with minor excipients as necessary to provide stability or pH balance during manufacturing, that delivers the drug in the lung and rapidly.(10)
Device (Inhaler System)
The Afrezza delivery system is a drug–device combination consisting of Technosphere insulin dry powder and a second-generation (Gen2) breath-powered inhaler developed by MannKind Corporation. The inhaler is a non-propelled, small handheld system, which provides a single puff of FDKP-containing insulin as it enters the lung via the patients inspiratory flow, via a prefilled single-use cartridge which is punctured when the lid is closed and produces an optimum 2-3 µm particle size which can be deposited in the alveoli, as current nebulisers and pressurised metered dose inhalers produce much larger particles which are unable to reach the deep lung (alveoli) effectively and thus will not have good systemic absorption. It is designed for simple, coordinated and consistent dosing and is thus suitable for prandial use with regular, daily insulin therapy.(8,11)
Dosing Principles
Dosing is aimed at the ultra-rapid onset/offset characteristics and is predominantly used for mealtime (prandial) glucose control, where administration at the onset of the meal, the onset is within ~12–15 min and duration of 2-3 h (12). It comes in fixed-dose cartridges (4, 8 and 12 U) which are put together in the appropriate dose (13). The initial dosage usually starts at 4 U with each meal for insulin-naive patients, followed by titrations guided by postprandial blood glucose control. Since Afrezza's absorption has a lower bioavailability than that of a subcutaneous insulin regimen, the dosage must be increased. In T1DM, this drug should be used with long-acting basal insulin and in T2DM, this can be given with oral hypoglycemic agents or solely on its own (13). Pre-medications and serial lung function tests (eg, FEV) are advised to be checked and performed periodically due to its route of administration, along with its contraindication property in asthma and COPD patients, because it is inhaled (14). On the whole, dosage is titrated, individualised and adjusted according to when meals are eaten to take advantage of the fast-acting and short duration of action.(15)
Fig 2: Afrezza cartridges showing dose strengths (4, 8, and 12 units). Created with BioRender.com.
PHARMACOKINETICS AND PHARMACODYNAMICS
Onset Of Action
Initial Response
The mean time to the first detectable effect was achieved 12-15 minutes after the administration of the first dose (4U, 12U or 48U) of inhaled insulin in type 1 diabetic patients.(12)
Peak Response
For inhaled insulin, the mean time to peak effect was 35, 45, and 55 min after a single dose of 4, 12, and 48 units, respectively, in patients with type 1 diabetes.(16)
Duration And Time For Peak Concentration
The mean time for the effect to return to baseline after 1 dose of inhaled insulin (4 units) in type 1 diabetics was 90 minutes; (12 units) was 180 minutes, and (48 units) was 270 minutes.
The time to peak plasma insulin levels was reduced following the transition of patients from SUBQ to mealtime inhaled insulin. The time to peak serum insulin levels in the patients studied was between 10 and 20 min after oral inhalation of inhaled insulin, ranging from 4 to 48 U.(17)
COMPARISON WITH OTHER HUMAN INSULINS
|
PARAMETER |
Inhaled Insulin (Human) |
Regular Insulin (U-100) |
Regular Insulin (U-500) |
NPH Insulin (Isophane) |
|
Route |
Inhalation |
Subcutaneous (SC) / IV |
Subcutaneous (SC) |
Subcutaneous (SC) |
|
Onset (Initial Response) |
~12 min |
~30 min (SC) |
< 30 min |
1-3 hours |
|
Time to Peak effect (Pharmacodynamic) |
35–55 min |
1.5–3.5 hours |
Similar to U-100 |
4-8 hrs |
|
Duration of Action |
90–270 min (1.5–4.5 h) |
~8 hours |
Up to 24 hours |
Intermediate (variable, typically ~14–24 h) |
|
Time to Peak Concentration (Tmax) |
10–20 min |
1.5–3 hours |
4–8 hours |
~4 hours (1–12 h range) |
|
Pharmacokinetic Profile |
Rapid absorption, early peak, short duration.(12,16,17)
|
Moderate onset and duration. (18) |
Slower onset, prolonged duration (basal + prandial).(18) |
Delayed onset, prolonged/intermediate action.(19) |
Table 1: Pharmacokinetic and pharmacodynamic comparison of Afrezza and subcutaneous insulins.
Afrezza has a quicker onset and peak than subcutaneous insulin preparations and therefore allows better control of early postprandial glucose. A shorter duration of action decreases late postprandial hypoglycemia but has the drawback that longer-term control cannot be achieved. This suggests that Afrezza can act as a mealtime prandial insulin but is not yet an adequate substitute for long-acting insulin regimens.
CLINICAL EFFICACY IN POSTPRANDIAL GLUCOSE CONTROL
Key Clinical Trials
|
Trial |
Study Design & Sample Size |
Comparator |
PPG Reduction |
HbA1c Outcome |
Conclusion |
|
Bode et al., 2015 (AFFINITY-1) |
Randomised, open-label trial; Type 1 DM (n=345) |
Afrezza (inhaled insulin) vs Insulin Aspart (standard rapid-acting injected insulin) |
Reduces to ~30–50 mg/dL: Afrezza reduces early post-meal spikes faster due to rapid lung absorption |
HbA1c reduces to ~0.21% in the case of Afrezza vs ~0.40% (aspart): slightly less reduction overall |
Afrezza exhibits less late post-meal hypoglycemia and acts more quickly, controlling the initial glucose spike better. However, a shorter duration results in somewhat less total HbA1c decrease.(20) |
|
Julio Rosenstock et al., 2015 (AFFINITY-2) |
Randomised, double-blind trial; Type 2 DM uncontrolled on oral drugs (n=353) |
Afrezza + Oral Antidiabetics vs Placebo + Oral Antidiabetic drugs |
Reduces to ~40–60 mg/dL: significant reduction in post-meal glucose vs placebo |
HbA1c reduces~0.82% vs ~0.42% (placebo): clinically meaningful improvement |
Demonstrates that co-administration of Afrezza improves overall and postprandial glycemic control; supports the utility of Afrezza as an add-on therapy for Type 2 Diabetes.(21) |
|
McGill et al., 2020 |
Randomised c ontrolled trial; Type 1 DM (n=138) |
Afrezza vs Subcutaneous Rapid-acting Insulin (Lispro).
|
Significant reduction in early PPG (0–90 min); lower glucose AUC in first 60–90 min with Afrezza (~15–25% lower early exposure) |
HbA1c reduction: similar between groups (~0.6 to −0.7%) |
The Afrezza counteracts this initial rise in postprandial glucose with a faster time course of insulin action but achieves comparable HbA1c levels to lispro by its time-limited effect.(22) |
|
Akturk et al., 2018 |
Randomised CGM-based interventional study; Type 1 DM (n=60) |
Afrezza vs Subcutaneous Rapid-acting Insulin |
Marked decrease in postprandial glucose excursions; predominantly during the first 1-4 hours after meals, suggesting good management of glucose excursions. |
Minimal or no significant difference in HbA1c between groups |
Improved daily glucose stability compared to the current regimen over postprandial hyperglycemia and hyperglycemia, without causing hypoglycemia, but achieves comparable HbA1c levels.(23) |
Table 2: Key clinical trials of Afrezza in diabetes.
Studies consistently demonstrate that Afrezza affords better initial postprandial glucose control because of its faster onset profile than S.C. Insulin. Nevertheless, its effect on HbA1c is typically equivalent to or less than s.c. Insulin, due to its short duration of action, is therefore a useful alternative in controlling the postprandial glucose rise.
COMPARATIVE EFFECTIVENESS
Afrezza vs Subcutaneous Rapid-Acting Insulin
|
Parameter |
Afrezza (Inhaled Insulin)
|
Subcutaneous Rapid-Acting Insulin (e.g., insulin aspart) |
Explanation |
|
ADVANTAGES |
|||
|
Onset of Action |
~12–15 min
|
~30–45 min |
Afrezza has around 15–20 min faster onset, which is better control of early post-meal spike (0–60 min).(21) |
|
Time to Peak
|
~35–45 min.(16) |
~60–120 min.(24) |
An earlier peak that coincides with the post-meal physiological insulin spike. |
|
Physiological Insulin Mimicry
|
High (close to first-phase insulin response) |
Moderate (delayed absorption) |
Afrezza reproduces first-phase insulin release, which normally occurs within minutes after eating; injected insulin misses this early spike. Afrezza leads to better early glucose handling.(20) |
|
LIMITATION |
|||
|
Dosing Flexibility
|
Fixed doses (4, 8, 12 units) |
Flexible titration |
Limited precision → possible under/over correction.(22) |
|
Variability Parameter |
|||
|
Early Postprandial Variability (0–1 hr) |
Significantly reduced (smaller glucose spikes) |
Higher variability due to delayed onset |
Better early glucose stability is offered with Afrezza.(22) |
|
Peak Glucose Excursion |
Lower peak glucose levels |
Lower peak glucose levels |
Reduced oxidative stress and glucose swings. (23) |
|
Late Postprandial Variability (2–4 hr) |
Slightly higher (short duration) |
More stable control |
Subcutaneous Rapid-Acting Insulins work best for prolonged effects.(20) |
|
Time in Range (TIR) |
Increased (~62%) |
Lower (~54%) |
More time in the target range, which helps improve control. |
|
Time Above Range (TAR) |
Reduced (~34%) |
Higher (~41%) |
Less hyperglycemia with Afrezza.(23) |
|
Hypoglycemia Variability |
Reduced late hypoglycemia |
Higher late hypoglycemia |
Safer late post-meal profile.(20) |
|
Glucose Exposure (AUC) |
Lowers early AUC (~15–25% reduction) |
Higher early exposure |
Less early glucose fluctuation with Afrezza. |
|
Overall Glycemic Variability Pattern |
Rapid rise & fall, less prolonged fluctuation |
Slower onset, prolonged glucose elevation |
Afrezza improves short-term variability, SC insulin improves long-term stability.(22) |
Table 3: Afrezza vs rapid-acting insulin: comparative effectiveness.
The advantages of Afrezza are increased initial glycemic control, decreased glucose variability, and improved time-in-range over subcutaneous rapid-acting insulin. The faster absorption of Afrezza is closer to endogenous insulin release and therefore better controls early postprandial glucose peaks. This faster action, however, may lead to less durable control late in the postprandial state.
SAFETY AND TOLERABILITY
Common Adverse Effects
|
System |
Adverse Effect |
Incidence |
|
Common (> 10%) |
||
|
Endocrine and Metabolic |
Hypoglycemia |
67% |
|
|
Severe hypoglycemia |
5% |
|
Respiratory |
Cough |
26% |
|
Less Common (1-10%) |
||
|
Gastrointestinal |
Diarrhea |
3% |
|
|
Nausea |
2% |
|
Nervous System |
Fatigue |
2% |
|
Respiratory |
Productive Cough |
2% |
|
Postmarketing Reports |
||
|
Respiratory |
Bronchospasm |
|
Table 4: Adverse effects of Afrezza.
Hypoglycemia predominates among the adverse effects of Afrezza, as expected with insulin, and severe hypoglycemia is less commonly seen. Cough is the most frequent non-metabolic adverse event as a consequence of the inhalational form of the drug. The most common other adverse effects are mild gastrointestinal discomfort and fatigue. However, for respiratory system adverse events (such as post-marketing reports of bronchospasm), attention must be paid to those patients who have lung disease.(16,25)
Contraindications
- Afrezza is not recommended for the management of diabetic ketoacidosis
- Patients with chronic lung disease, including asthma and COPD, are contraindicated from using Afrezza.
- Smokers (including recently stopped smokers) are contraindicated from Afrezza
- People hypersensitive to insulin and Afrezza excipients are contraindicated from using Afrezza.(26)
Pulmonary Function Monitoring (FEV1)
Afrezza causes a stepwise decline in pulmonary function, determined by Forced expiratory volume 1 sec (FEV1). If the FEV1 of the patient has a more than 20% reduction from baseline, then discontinue Afrezza.(27)
Spirometry tests need to be done periodically, regardless of whether the patient has pulmonary symptoms. More investigation is needed in order to determine the long-term two-year efficacy of Afrezza in lung function and the reversibility of FEV1 changes after cessation.(14)
PATIENT-CENTERED OUTCOMES
Afrezza (Technosphere inhaled insulin) is highly patient-centred as evidenced by its convenience, needle-free nature, and treatment satisfaction (12,28). Patients accept therapy more easily because it avoids needles and the needle-associated problems of discomfort, anxiety, and the general bad perception of injections (28). On the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and patient satisfaction with insulin therapy (PSIT), Afrezza shows improvements in patient satisfaction regarding convenience, Ease of use and Patient Choice (improvement of 30-40% compared with subcutaneous insulin). The result is improved compliance and persistence as decreased treatment burden and increased satisfaction encourage continuous insulin therapy. In summary, Afrezza increases quality of life and long-term diabetes control.(20,29)
SPECIAL POPULATIONS AND CLINICAL CONSIDERATIONS OF AFREZZA
Type 1 vs Type 2 Diabetes
Afrezza can be taken by patients with type 1 and type 2 diabetes mellitus at the age of adulthood. Type 2 diabetes can be treated with oral antidiabetic drugs or basal insulin alone or in combination with Afrezza; while for type 1 diabetes, to provide adequate control of glucose, patients must receive Afrezza with a long-acting basal insulin. Existing clinical studies confirm that, despite its equal efficacy in glycaemic control in type 1 subjects when given via the subcutaneous route, subcutaneous rapid-acting insulin leads to a significantly better control of postprandial glycaemia in type 2 individuals.(20)
Smokers
Afrezza must be withheld in smokers and former smokers as the absorption of inhaled insulin in the lungs can be influenced greatly by cigarette smoking. This will predispose to unwanted side effects and cause unpredictable serum drug levels. Patients are generally required to abstain from smoking prior to initiation and during therapy.(30)
Patients With Lung Disease
Patients with long-term lung conditions like asthma or COPD shouldn't take afrezza because it may result in an unintended bronchospasm. Safety concerns over lung usage are the priority for Afrezza because it is administered by inhalation. Pulmonary function tests (FEV etc) should be performed before and during treatment regularly. Monitoring is encouraged as slight decreases in lung function have been reported in clinical trials.
Pediatric Population
Afrezza is presently only authorised for use in adults, and its safety and effectiveness in paediatric patients have not been established. The clinical significance in children and adolescents with diabetes is being evaluated in clinical trials, but should not be utilised until sufficient data have been accumulated.(16)
Geriatric Population
Afrezza can be administered in elderly people, although care must be taken because of age-related lung function reduction and a higher risk of hypoglycemia. For this population, it is very important to individualise the dose and to monitor the patient carefully. The dose should be chosen on clinical judgment, and no specific fixed change in the dose is needed.(16,21)
LIMITATIONS
- Respiratory adverse events:
Frequent adverse events, such as cough, sore throat and some other mild respiratory irritation, may cause discomfort to the patient and affect compliance.
- Not appropriate for use in pulmonary conditions:
Afrezza may decrease lung function and induce bronchospasm; it is not advised to take it in asthma and COPD.
- Not recommended for smokers:
Smoking affects the absorption of insulin in the lungs and, therefore, limits its use in this population because of uncertain kinetics and reduced safety.
- Low generalizability of trial data:
Results may not be completely applicable to a general population, since high-risk groups (e.g., smokers and people with existing lung disease) were not included in trials.
- Variable absorption:
The potentially uneven absorption of insulin from pulmonary delivery, as opposed to injection in subcutaneous fat, could affect glucose control.
- Practicality and market restrictions:
The market for early inhaled insulin devices was disappointing, and they were subsequently withdrawn due to these clinical and usability limitations.
- Uncertainty in long-term safety:
There is minimal data on prolonged exposure to the lungs, and concerns are present about the potential for chronic pulmonary effects, possibly lung function decline.(31)
- Device dependence:
Need for device dependence and correct inhalation technique; mistakes here will lessen effectiveness.
- Monitoring burden:
Spirometry is needed at baseline and also regularly, which increases the workload of clinic staff.(30)
- Costly:
More costly than the short-acting subcutaneous insulin.(32)
FUTURE PERSPECTIVES
Advances In Inhaled Insulin Technology
Microparticles of FDKP were the basis for the quick absorption of insulin through the lung for Afrezza (Technosphere insulin). New technology advancements are expected to include: enhancement of deposition in the lung, dose consistency, and reliable delivery. A number of novel techniques and designs, including smart / breath-actuated inhalers, glucose-responsive insulin, and nanoparticle-based delivery, are expected to improve the efficacy and decrease variable delivery of inhaled insulin. Additionally, increased integration with mobile devices and reductions in the size of the devices are expected to improve compliance and provide a modern, integrated approach to diabetes.(28)
Role In Personalised Medicine
The very short duration and ultra-fast onset of Afrezza is advantageous for individualisation of diabetes therapy; it allows meal-time dosing that can be adjusted for response and lifestyle, beneficial in suppressing postprandial glucose, reducing the likelihood of delayed hypoglycemia, and allowing adjustment in erratic meal pattern individuals. Inter-patient variation necessitates individualisation, and combination with future AI methodologies may further optimise dosing by incorporating behavioural input with glucose data.(32,33)
Integration With Cgm And Digital Health
CGM and Afrezza: The creation of Afrezza, along with CGM, is a revolution in diabetes treatment. The continuous glucose monitor gives an instantaneous glucose reading and rapid-acting insulin with Afrezza, allowing the patient to respond to post-meal hyperglycemia promptly. With CGM's instant glucose readings and Afrezza's rapid-onset action, the user has the ability to quickly respond to post-meal hyperglycemia. It is expected that integration will take the form of:
- Closed-loop (artificial pancreas) systems, whereby CGM readings are used to determine insulin delivery.
- Hybrid systems consisting of a basal insulin pump plus meal-time use of inhaled insulin.
- Ongoing monitoring and decision support with the use of mobile health systems and cloud-based analytics.
Afrezza's fast pharmacodynamics may be beneficial in improving time-in-range and decreasing variability in glucose levels by attenuating delayed-acting insulin delivery, which is a major disadvantage of existing automated insulin delivery systems.(34)
CONCLUSION
Afrezza has been an excellent advance in insulin therapy in overcoming the significant unmet need in improving the postprandial hyperglycemia control with the fast-acting, physiologic profile of an insulin mimetic. Unlike subcutaneous rapid-acting insulin, the needle-free, noninvasive method of delivery enables better postprandial control, less variability, and greater patient satisfaction earlier in postprandial control. Nevertheless, the practical use of Afrezza is constrained by pulmonary concerns, smoking and patients with underlying chronic lung disease being excluded, the erratic absorption and continuous pulmonary monitoring needs. The key benefit is better control of postprandial glucose excursion and time-in-range, although the change in HbA1c is similar to standard therapy. Therapeutic applications of Afrezza could be greatly augmented with future advancements enabling individualised management strategies and combined with the use of continuous glucose monitoring systems. The concluding sentence from the paper declares: Afrezza is a valuable part of the anti-diabetic armoury of selected patients who might benefit from rapid prandial insulin action and increased treatment adherence without any compromise in safety profile.
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