Inhaled Insulin Research Articles

The Role of Pulmonary Drug Delivery in Modern Therapeutics: An Overview.

The pulmonary drug delivery system is a promising and evolving technology in which the prescribed medicine is breathed through the lungs, and subsequently, it enters the circulation via the alveolar epithelium. This category of pulmonary drug delivery system is an appealing and non-invasive administration method. Pulmonary drug delivery is most commonly utilized to treat airway problems by providing locally active medicines directly to their site of action. The dose required to have a pharmacological effect is reduced when medicines are delivered directly to their site of action. In addition to locally acting medications, the pulmonary route can be utilized to deliver compounds with systemic effects, such as in the case of insulin inhalation therapy for systemic absorption. Particle size, bioavailability, device compatibility, and other aspects must be addressed, including the formulation of drugs into an acceptable dosage for inhalation with sufficient stability. This formulation must also be used in conjunction with a suitable inhaler device that produces an aerosol with a particle or droplet size that assures deposition in the required targeted area of the pulmonary system. Recent advancements in pulmonary drug delivery include the development of targeted nanoparticles and inhalable biologics, which enhance drug absorption and efficacy while minimizing systemic side effects. Future directions focus on personalized medicine approaches and advanced inhalation technologies, although limitations such as variable patient adherence and the need for precise dosing continue to pose challenges.

IDF23-0336 Why has not inhalable insulin been adhered in Brazil?

IDF23-0336 Why has not inhalable insulin been adhered in Brazil?

New Routes of Insulin for Diabetes Treatment

Diabetes is a chronic condition marked by insufficient insulin production and the subsequent hyperglycemia. Optimal diabetes control has an impact on both microvascular and macrovascular disease, which are both diabetic consequences. Subcutaneous insulin injections or continuous infusions are frequently used by people with diabetes to manage their blood sugar levels. Given that insulin injection therapy is difficult for many patients, novel routes of insulin administration are of interest in the diabetes sector. Inhalational insulin administration will be covered in this review. The effectiveness of inhaled insulin in comparison to subcutaneous insulin in the various populations with diabetes iscovered, as well as its safety. Additionally, the experience and challenges associated with the creation and promotion of insulin for inhalation are reviewed.

Transforming Evidence Generation for Drug Label Changes: A Case Study.

Computer Modeling and Simulation (CM&S) provides the opportunity to drastically reduce clinical trial patient burden and advance regulatory decision making. At the suggestion of the US Food and Drug Administration (FDA), MannKind Corporation and Nudge BG submitted an application to the FDA Model-Informed Drug Development (MIDD) pilot program to support a label change for the initial dose of Afrezza® (insulin human), a novel inhalable insulin with a rapid pharmacokinetic and pharmacodynamic profile. The MIDD pilot program demonstrates the FDA's commitment to advancing regulatory science through the adoption of evidence generated by CM&S. A simulation framework was developed based on empirical data. It was used to generate evidence to support the label change. Briefing packages and presentations were prepared for two meetings with the FDA, over a period of four months. The model was thoroughly characterized, determined to be low risk for the question of interest, and submitted along with additional clinical evidence for validation. The FDA found the simulation framework to be helpful in providing insights into the question of interest and provides reasonable glycemic outcome predictions. At the conclusion of the MIDD paired meetings, FDA personnel from the Center for Drug Evaluation and Research review team accepted the simulation and requested additional, traditional clinical evidence to support the proposed label change. In the post-meeting comments, the FDA invited MannKind to submit a proposal for a data package including the CM&S evidence in a Type C meeting for further discussion on the label change. This MIDD pilot experience suggests that CM&S is a credible method for evidence generation. Collaboration between sponsor organizations as well as all stakeholders in the FDA, including proponents of CM&S, can further support regulatory decision-making. The learnings from early participants will allow the program to reach its full potential and thereby ultimately benefit patients, sponsors, and FDA.

Integrated Continuous Crystallization and Spray Drying of Insulin for Pulmonary Drug Delivery

Pulmonary delivery of insulin in the form of a dry powder is an attractive alternative in comparison to conventional subcutaneous delivery. Insulin crystals have potential advantages such as sustained release and higher stability in comparison to amorphous particles. However, the design of crystallization processes that can reliably produce insulin crystals in a suitable size range for pulmonary delivery is challenging. A continuous process involving the integration of a tubular crystallizer and a spray dryer is characterized for the production of inhalable insulin. Supersaturation is created via cooling and a pH shift at the inlet of the crystallizer, aiming at a high nucleation rate. The recovery of insulin in the crystallizer exceeds 90%, and the insulin particles appear crystalline under most of the tested conditions. Integration with a spray dryer produces a dry powder with favorable properties for pulmonary drug delivery. The emitted fraction of insulin from a capsule in a commercial inhaler is in the range of 84.3–93.1%, which shows good powder dispersibility. Furthermore, the fine particle fraction of the insulin crystals ranges from 22.0% to 36.4%, which indicates a good potential for pulmonary delivery.

Protective Effect of Nedocromil Against Insulin Induced Airway Hyper-Reactivity

Background: Use of inhalable insulin is limited because it causes airway hyper-reactivity. So present study was designed to ameliorate inhalational insulin induced airway hyper-responsiveness.Objectives: The objective of the study was to evaluate the acute effects of insulin on airway reactivity and protective effects of nedocromil against insulin induced airway hyper-reactivity on isolated tracheal tissues of guinea pigs in vitro.Material and Methods: This experimental study was carried out in Pharmacology department of Army Medical College Rawalpindi from January 2012 to July 2012. We observed acute effect of insulin (10-7- 10-3 M) and insulin pretreated with nedocromil (10-5 M) on isolated tracheal strip of guinea pig (n=6) in vitro by constructing cumulative concentration response curves. The tracheal smooth muscle contractions were recorded with Transducer on Four Channel Oscillograph.Results: Insulin significantly increased the tracheal smooth muscle contraction. The mean ± SEM of maximum amplitudes of contraction with insulin and insulin pretreated with nedocromil were 35 ± 1.13 mm and 27.8 ± 1.27 mm respectively. So nedocromil significantly antagonized insulin elicited contractile effect. Conclusion: Nedocromil significantly inhibited the insulin mediated airway hyper-reactivity in guinea pigs. So we suggest that pretreatment of inhaled insulin with nedocromil may have clinical implication in amelioration of its potential respiratory adverse effects.

A Review: The Prospect of Inhaled Insulin Therapy via Vibrating Mesh Technology to Treat Diabetes.

Background: Inhaled insulin has proven to be viable and, in some aspects, a more effective alternative to subcutaneous insulin. Past and present insulin inhaler devices have not found clinical or commercial success. Insulin inhalers create a dry powder or soft mist insulin aerosol, which does not provide the required uniform particle size or aerosol volume for deep lung deposition. Methods: The primary focus of this review is to investigate the potential treatment of diabetes with a wet insulin aerosol. Vibrating mesh nebulisers allow the passive inhalation of a fine wet mist aerosol for the administration of drugs to the pulmonary system in higher volumes than other small-volume nebulisers. Results: At present, there is a significant focus on vibrating mesh nebulisers from the pharmaceutical and biomedical industries for the systemic administration of pharmaceuticals for non-traditional applications such as vaccines or the treatment of diabetes. Systemic drug administration using vibrating mesh nebulisers leads to faster-acting pharmaceuticals with a reduction in drug latency. Conclusions: Systemic conditions such as diabetes, require the innovative development of custom vibrating mesh devices to provide the desired flow rates and droplet size for effective inhaled insulin administration.

1019-P: Variability of 501 Inhaled Insulin Absorption and Action

501 inhaled insulin (INH) is a novel liquid formulation of human insulin for inhalation with faster onset of action than s.c. insulin lispro (LIS). This randomized, replicated cross-over trial investigated the variability of INH vs. LIS during 10-hour glucose clamps in non-smoking subjects with T1D. Fourteen subjects (age [mean±SD] 32.5±7.9 years, BMI 26.5±2.1 kg/m2, HbA1c 7.5±0.8 %) received 2 single doses of 92.2 IU INH via the Afina inhaler (n=13 completing subjects) and 2 injections of an equivalent 12 U LIS dose (n=12). The inhalations were performed by the subjects after a brief training on the correct inhalation technique; injections were given by trained staff. Repeated dosing of INH by the same subject resulted in reproducible insulin absorption and insulin action, with lower or similar variability vs. LIS (Table 1). The response to INH between subjects was more variable than for LIS. The 13.8±8.1% mean relative biopotency of INH was consistent with previous findings. INH was well tolerated, adverse events (8 with INH, 13 with LIS) were mild to moderate in severity. No cough and no acute changes in spirometry were observed with any inhalation. In conclusion, the intra-individual response to self-administration of 501 inhaled insulin is as reproducible as that of s.c. insulin lispro injected by experienced staff. This is a clinically meaningful outcome and enables individual dose titration of 501 insulin in future treatment. Disclosure E. Zijlstra: Employee; Self; Profil. Speaker’s Bureau; Self; Aerami Therapeutics, Eli Lilly and Company, Novo Nordisk A/S. G. Andersen: Employee; Self; Profil Institute for Clinical Research. L. Plum-Moerschel: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk A/S. M. Rhodes: None. R. Patton: None. B. Bueche: None. M. Kuo: None. T.H. Le: None. B.J. Stedman: None. J.S. Patton: Board Member; Self; Dance Biopharm Holdings, Inc.

INSULINA INALÁVEL: UMA ROTA TERAPÊUTICA SEGURA?

O diabetes mellitus é uma doença causada pela deficiência relativa ou absoluta do hormônio insulina, manifestando complicações macrovasculares e microvasculares em decorrência da hiperglicemia. Desde o primeiro uso de insulina subcutânea novas rotas foram pesquisadas tendo destaque a via pulmonar que é menos invasiva e mais cômoda. Diante disso, este trabalho levanta algumas considerações sobre a segurança clínica da insulina inalável Afrezzaâ, recentemente aprovada para comercialização no Brasil. Para isso, foi realizado estudo de revisão da literatura relacionado à insulina inalável, mediante busca eletrônica de artigos indexados na base de dados online SCIELO. Concisamente, os trabalhos relataram que a absorção da insulina por via pulmonar permite um início de ação mais rápido e uma duração de ação mais curta em relação aos análogos de insulina subcutânea. Os efeitos adversos mais comuns associados ao produto Afrezza® foram tosse, hipoglicemia, irritação da garganta e episódios de broncoespasmo agudo em pacientes asmáticos. Ainda assim, a insulinoterapia por via inalável representa um importante avanço para a reposição de insulina exógena, especialmente por dispensar o uso de agulhas. Contudo, o uso da insulina Afrezza® por pacientes com doença pulmonar prévia deve ser ponderado, particularmente pelo possível risco associado a incidência de tumores no trato respiratório.

Recent Advances in Inhaled Formulations and Pulmonary Insulin Delivery Systems.

Insulin (INS) therapy played a great role in patients with type 1 and type 2 diabetes to regulate blood glucose levels. Although hypodermic injection was commonly used for insulin delivery, it had some disadvantages such as pain, needle phobia and the risk of infection. Therefore, pulmonary insulin delivery had been developed as an alternative method to overcome the therapeutic challenges in recent years since pulmonary insulin administration showed great improvements in rapid action and circumvention of first-pass hepatic metabolism. This review described the most recent developments in pulmonary insulin administration. Firstly, the structure and physiology of the lung cavity were introduced. Next, the advantages and disadvantages of pulmonary administration were discussed. Then some new dosage forms for pulmonary insulin were investigated including carriers based on surfactants and carriers based on polymers. Finally, innovate insulin inhalers and formulations were also described.

Biosynthetic Human Insulin and Insulin Analogs.

Biosynthetic human insulins and analogs have replaced animal insulins and permitted structural modifications to alter the rate of absorption, duration of action, improve reproducibility of effects, and modulate relative efficacy in various target tissues. Several forms of rapidly acting insulins nearly achieve rapid pharmacokinetics and pharmacodynamics similar to first-phase insulin release. There is need for even faster-acting analogs to mimic normal physiology and improve control of postprandial glycemic excursions. Two biosynthetic insulin analogs have sufficiently long duration of action for use as once-daily basal insulins; controversy persists regarding their respective risks of hypoglycemia and relative glycemic variability. Basal-bolus therapy and insulin pump therapy, including closed-loop automated insulin delivery, require rapid-acting insulin analogs. The longer acting insulins can provide stable, reproducible basal insulin with reduced rates of hypoglycemia, particularly nocturnal hypoglycemia, greater efficacy in reducing mean glucose and glucose variability while increasing time in glucose target range. Inhalable human insulin provides very rapid action. Premixture of rapid-acting analogs with protamine has been useful for some patients with type 2 diabetes. An insulin analog with preferential efficacy at the liver has been developed and tested clinically but not marketed. Current research is aimed at developing even faster-acting insulin analogs. Long-acting basal insulins coformulated with GLP-1 receptor agonists or with a rapidly acting insulin analog have valuable clinical applications. Excipients, chaperones, local heating of the infusion site, and hyaluronidase have also been used to accelerate the absorption of insulin analogs. Biosynthetic human insulins have radically revolutionized management of both type 1 and type 2 diabetes worldwide. The ability to manipulate the structure and formulation of insulin provides for more physiologic pharmacokinetics and pharmacodynamics, enabling improved glycemic control, reduced risk of hypoglycemia, and reduced rates of long-term complications.

Nanotechnology Advanced Strategies for the Management of Diabetes Mellitus.

Medications currently available for the management of diabetes mellitus are inconvenient and have some limitations. Thus, investigations for novel approaches are needed to deliver and target antidiabetics safely to the site of action. The present review emphasizes the limitations of conventional antidiabetics and provides the recent progresses of nanotechnology in the treatment of diabetes mellitus with a special highlight on the novel nanocarriers methodologies employed as antidiabetic drug delivery systems. The potential nanocarriers employed for the treatment of diabetes comprise liposomes, niosomes, self-nanoemulsifying drug delivery systems, polymeric nanoparticles, gold nanoparticles, dendrimers and micelles. Herbal nanomedicine has also emerged to be a promising way for adequate delivery of herbal compounds. Other nanotechnology approaches involve the usage of oral insulin, inhalable insulin, artificial pancreas, and nanopump. Nanocarriers have proved to lead a successful delivery of antidiabetic medications, aiming at drug targeting for enhanced efficacy and safety. These innovative generations of drug delivery systems have important benefits over conventionally existing ones. The future of nanotechnology in the management of diabetes is still open with several prospects and will be of pronounced significance.

RECENT ADVANCES AND FUTURE PROSPECTS OF NON-INVASIVE INSULIN DELIVERY SYSTEMS

Non-invasive insulin delivery systems have been of global interest. The goal of many studies was to optimize suitable delivery formulation capable of producing comparable insulin bioavailability and safety that match or supersedes conventional delivery by the invasive subcutaneous (SC) injections. Historically, Pfizer marketed the first insulin inhaler Exubera® in 2006 which was later retracted from the market before completing the two years. In recent years, Afrezza®, a new inhalator, and Oral-Lyn™, a buccal spray, have been introduced to the market. While Afrezza® lost the marketing and distribution support from Sanofi, Oral-Lyn™ have not secured US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) marketing approval yet. Different technologies to improve insulin’s permeation and absorption through different routes are in the pipelines. This review discusses several non-invasive strategies that have been appropriately tested and duly approved by the FDA. Other delivery systems are in different phases of development, ranging from in vitro studies to phase 3 clinical trials, providing indications towards the prospects of next-generation delivery systems. This review covers studies published in the past 10 y using Scopus, Clinicaltrials.gov, PubMed and Google scholar databases. The outcomes of this review indicate that the door is still open for more innovative, efficient and convenient non-invasive insulin delivery systems than currently available which may take several years before we can see a game changer in the market.

Improved Time-in-Range (TIR) on Continuous Glucose Monitor (CGM) with Technosphere Inhaled Insulin (TI) Compared with Insulin Aspart in T1D Patients—STAT Study

Sixty patients with T1D on multiple daily injections (MDI) were randomized in a multi-center study, stratified by A1c values (<8.5% or ≥ 8.5%) to the control arm using aspart (n=34) vs. TI group (n=26). Patients in the TI arm were advised to take extra inhalations at 1 and 2 hours after meals based on post-prandial blood glucose (PPBG) values. Baseline characteristics and FEV1 were similar. Using per protocol (PPT) analysis, we examined outcomes over the 4-week period using linear regression with repeated measures. The primary outcomes were TIR (70-180 mg/dL) and PPBG excursions. Compliance with TI was based on its use when indicated at 1- and 2-hour PPBG. Patients with at least 80% compliance were included in PPT (n=15). Seven TI patients were non-compliant; 2 dropped out of the study; and 2 did not have CGM data. CGM glucose patterns and TIR for a patient with 100% or with 56% compliant with TI are shown (Figure 1a and 1b). TIR was significantly higher in the TI-compliant group compared to control or TI-non-compliant groups (Figure 1c). PPBG was also significantly lower in the TI-compliant compared to the control group at 1- and 2-hours post-prandial but not at 3 and 4 hours. PPBG was significantly lower in the compliant vs. non-compliant TI group at all time points (Figure 1d). We conclude that TI improves TIR and PPBG values, if patients use additional inhalations as directed. Disclosure J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation. H.K. Akturk: None. A. Rewers: None. B.W. Bode: Research Support; Self; Abbott. Advisory Panel; Self; ADOCIA. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk Inc., Diasome Pharmaceuticals, Inc., Sanofi US, Eli Lilly and Company, MannKind Corporation, Dexcom, Inc., OmniPod, Senseonics. L.J. Klaff: Research Support; Self; Abbott, Intarcia Therapeutics, Inc., MannKind Corporation, Dexcom, Inc., Novartis Pharmaceuticals Corporation, Gelesis, Novo Nordisk Inc., Eli Lilly and Company, Medtronic, Sanofi. A. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical. Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Eli Lilly and Company, Insulin Algorithms, JDRF, Lexicon Pharmaceuticals, Inc., Livongo Health. Research Support; Self; MannKind Corporation. Other Relationship; Self; Medscape. Advisory Panel; Self; Merck & Co., Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Omada Health, Inc., Optum Rx, Inc., Sanofi. Research Support; Self; T1D Exchange. Advisory Panel; Self; The Endocrine Society. Research Support; Self; The Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; Spouse/Partner; Johnson & Johnson Diabetes Institute, LLC. T.S. Bailey: Research Support; Self; Abbott. Consultant; Self; Abbott. Speaker's Bureau; Self; Abbott. Research Support; Self; Ambra BioScience, Ascensia Diabetes Care, Becton, Dickinson and Company. Consultant; Self; Becton, Dickinson and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical. Consultant; Self; Calibra Medical. Research Support; Self; Companion Medical, Dexcom, Inc., Glooko, Inc., GlySens Incorporated, Lexicon Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Medtronic MiniMed, Inc.. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Senseonics. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Versartis, Inc., Xeris Pharmaceuticals, Inc., MannKind Corporation. S.K. Garg: Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Sanofi US. Advisory Panel; Self; Sanofi US. Research Support; Self; MannKind Corporation, Diasome Pharmaceuticals, Inc., Labstyle Innovations, Lexicon Pharmaceuticals, Inc., Medtronic. Advisory Panel; Self; Novo Nordisk A/S.

Improved Postprandial Blood Glucose (PPBG) Excursions with Technosphere Inhaled Insulin (TI) Compared with Aspart in T1D Patients—STAT Study

Post-prandial hyperglycemia is difficult to control due to lack of an ideal prandial insulin. TI (Afrezza®) has the most rapid onset of action, lasts for 2 hours. Sixty patients with T1D on multiple daily injections (MDI) were randomized in a multi-center study, stratified by baseline A1c values (<8.5% or ≥ 8.5%) to the control group using aspart (n=34) vs. TI group (n=26). The TI arm was advised to take extra inhalations at 1 and 2 hours after meals based on PPBG. Baseline characteristics were similar (Figure 1a). Forced Expiratory Volume did not differ at all times. We used intent-to-treat analysis, and examined outcomes over a 4-week period using linear regression with repeated measures. Mean CGM glucose, SD, time in range (70-180 mg/dL), % time in hyper- (>180 mg/dL) or hypoglycemia (<70, <60, or <50 mg/dL) were similar in both groups. PPBG at 1 hour was lower in the TI group (mean ± SE PPBG difference -31.7±6.6 mg/dL, p<0.0001). PPBG was numerically lower at 2 hours (mean ± SE PPBG -13.0±7.1 mg/dL, p=0.07) with no difference at 3 and 4 hours (Figure 1b). The TI group increased bolus insulin dose (mean ± SD of 47.8 ± 23.9 U/day) compared to the control group (23.0 ± 9.8 U/day; p<0.0001) in week 1. Bolus insulin dose in the TI group was higher (28.2 U/day; p<0.0001), and did not differ by study week (p=0.25). We conclude that TI improves PPBG when treat-to-target algorithms are used in patients with T1D on MDI. Disclosure H.K. Akturk: None. J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation. A. Rewers: None. L.J. Klaff: Research Support; Self; Abbott, Intarcia Therapeutics, Inc., MannKind Corporation, Dexcom, Inc., Novartis Pharmaceuticals Corporation, Gelesis, Novo Nordisk Inc., Eli Lilly and Company, Medtronic, Sanofi. A. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical. Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Eli Lilly and Company, Insulin Algorithms, JDRF, Lexicon Pharmaceuticals, Inc., Livongo Health. Research Support; Self; MannKind Corporation. Other Relationship; Self; Medscape. Advisory Panel; Self; Merck & Co., Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Omada Health, Inc., Optum Rx, Inc., Sanofi. Research Support; Self; T1D Exchange. Advisory Panel; Self; The Endocrine Society. Research Support; Self; The Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; Spouse/Partner; Johnson & Johnson Diabetes Institute, LLC. B.W. Bode: Research Support; Self; Abbott. Advisory Panel; Self; ADOCIA. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk Inc., Diasome Pharmaceuticals, Inc., Sanofi US, Eli Lilly and Company, MannKind Corporation, Dexcom, Inc., OmniPod, Senseonics. T.S. Bailey: Research Support; Self; Abbott. Consultant; Self; Abbott. Speaker's Bureau; Self; Abbott. Research Support; Self; Ambra BioScience, Ascensia Diabetes Care, Becton, Dickinson and Company. Consultant; Self; Becton, Dickinson and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical. Consultant; Self; Calibra Medical. Research Support; Self; Companion Medical, Dexcom, Inc., Glooko, Inc., GlySens Incorporated, Lexicon Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Medtronic MiniMed, Inc.. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Senseonics. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Versartis, Inc., Xeris Pharmaceuticals, Inc., MannKind Corporation. S.K. Garg: Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Sanofi US. Advisory Panel; Self; Sanofi US. Research Support; Self; MannKind Corporation, Diasome Pharmaceuticals, Inc., Labstyle Innovations, Lexicon Pharmaceuticals, Inc., Medtronic. Advisory Panel; Self; Novo Nordisk A/S.

Recommendations for Initiating Use of Afrezza Inhaled Insulin in Individuals with Type 1 Diabetes

Treatment with Afrezza® (insulin human) inhalation powder in individuals with type 1 diabetes (T1D) reduces HbA1c levels similar to rapid-acting insulin analogs, but with significantly less hypoglycemia due to its unique time action profile. Examinations of studies of Afrezza pharmacokinetics/pharmacodynamics, relevant clinical trials, and U.S. Food and Drug Administration (FDA) documentation suggest that current FDA-mandated dosing recommendations for initiating Afrezza treatment may not result in optimal glycemic control for individuals with T1D. Recommendations for initiating Afrezza insulin therapy in T1D patients are presented in this article.

Hybrid Surface and Bulk Resonant Acoustics for Concurrent Actuation and Sensing on a Single Microfluidic Device.

While many microfluidic devices have been developed for sensing and others for actuation, few devices can perform both tasks effectively and simultaneously on the same platform. In piezoelectric sensors and actuators, this is due to the opposing operating requirements for sensing and actuation. Sensing ideally requires narrow resonant peaks characterized by high quality factors, such as those found in quartz crystals. However, these materials usually have poor electromechanical coupling coefficients that are not ideal for actuation. In this work, we show that it is possible to achieve both sensing and actuation simultaneously on a shared device by exploiting the distinct advantages of both bulk waves for effective mass sensing and surface waves for highly efficient microfluidic actuation through a unique hybrid surface and bulk acoustic wave platform. In light of the recent resurgence of interest in portable inhaled insulin devices for personalized diabetes management, we demonstrate the use of this technology for efficient aerosolization of insulin for inhalation without denaturing the protein, while being able to concurrently detect the residual mass of the un-nebulized insulin remaining on the device such that the actual dose delivered to the patient can be determined in real time.

Diabetes medication pharmacology

Diabetes medication pharmacology

Inhaled Insulin - Current Direction of Insulin Research.

Diabetes Mellitus (DM) is a metabolic disorder characterized by relative or absolute deficiency of insulin, resulting in hyperglycemia. Subcutaneous insulin and Oral Hypoglycaemic Agents (OHA) constitute the main treatment option for DM. Insulin is administered by injection or continuous infusion to control glucose levels mainly in Type I diabetes. Newer routes both oral and non oral, for insulin administration are current direction of insulin research as insulin injection therapy is burdensome and painful for many patients. Inhalational insulin is an attractive alternative for systemic administration of insulin given its accessibility and large alveolar-capillary network of lungs for drug absorption. Afrezza, inhaled insulin has been recently approved by Food and Drug Administration (FDA). It is a new, quicker acting inhalable insulin with a different and safer pharmacokinetic profile in comparison to previously failed inhaled form of insulin.

New Medications for the Treatment of Diabetes

New Medications for the Treatment of Diabetes