Future prospect of insulin inhalation for diabetic patients: The case of Afrezza versus Exubera

Al-Tabakha, Moawia M.

doi:10.1016/j.jconrel.2015.07.025

Cited by 54 publications

(22 citation statements)

References 64 publications

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“…It has been observed that one key aspect to this product's success is the manufacturer's on-going support and marketing to both consumers and providers [35]. Survey data suggest that providers would consider this alternative method of insulin delivery, but reserve it for specific patient populations.…”

Section: Place In Therapymentioning

confidence: 99%

The Role of Inhaled Insulin in the Management of Type 2 Diabetes

Nuffer¹,

Trujillo²

2016

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Type 2 diabetes continues to place a major burden on the health care system of the United States and worldwide. Type 2 diabetes involves two major defects: decreased insulin production from the pancreas and increased insulin resistance. Many patients with type 2 diabetes have decreased insulin production which requires exogenous insulin therapy in order to manage their disease. Despite this need, there is often a reluctance to initiate insulin therapy from both providers and patients. One reason for this reluctance may be a fear of needles or of administering injections. Delivering insulin through the lungs has been studied for decades, with the first inhaled insulin product coming to market in 2006. This product's launch was considered unsuccessful, and the product was discontinued by the manufacturer the following year. A new inhaled insulin, Technosphere ® insulin, was approved for use in type 1 and type 2 diabetes in 2014. This product was shown superior to placebo and non-inferior to a premixed bi-phasic subcutaneous insulin in patients with type 2 diabetes, and may offer an alternative to patients who are averse to giving subcutaneous injections.

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Section: Place In Therapymentioning

confidence: 99%

The Role of Inhaled Insulin in the Management of Type 2 Diabetes

Nuffer¹,

Trujillo²

2016

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“…Due to this difference in dynamics of insulin action and carbohydrate (CHO) absorption, attempts to avoid hyperglycemic peaks are usually accompanied by hypoglycemic excursions [10]. Several approaches have been tested to overcome such issue [11][12][13][14], but while an ultrarapid insulin analogue is not available [15], postprandial control using subcutaneous route will continue to be a challenging situation for closed-loop systems. Diverse studies have included estimations of insulin concentration in the body to avoid excessive insulin stacking [16][17][18][19]; however, hypo-and hyperglycemia are still a hazard for AP systems, and novel approaches are still required.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Rule-Based Algorithm to Tune Insulin-on-Board Constraints for a Hybrid Artificial Pancreas System

Bertachi

Biagi

Beneyto

et al. 2020

Journal of Healthcare Engineering

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The artificial pancreas (AP) is a system intended to control blood glucose levels through automated insulin infusion, reducing the burden of subjects with type 1 diabetes to manage their condition. To increase patients’ safety, some systems limit the allowed amount of insulin active in the body, known as insulin-on-board (IOB). The safety auxiliary feedback element (SAFE) layer has been designed previously to avoid overreaction of the controller and thus avoiding hypoglycemia. In this work, a new method, so-called “dynamic rule-based algorithm,” is presented in order to adjust the limits of IOB in real time. The algorithm is an extension of a previously designed method which aimed to adjust the limits of IOB for a meal with 60 grams of carbohydrates (CHO). The proposed method is intended to be applied on hybrid AP systems during 24 h operation. It has been designed by combining two different strategies to set IOB limits for different situations: (1) fasting periods and (2) postprandial periods, regardless of the size of the meal. The UVa/Padova simulator is considered to assess the performance of the method, considering challenging scenarios. In silico results showed that the method is able to reduce the time spent in hypoglycemic range, improving patients’ safety, which reveals the feasibility of the approach to be included in different control algorithms.

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“…The controlled release of insulin in response to blood glucose has the potential to significantly improve the health outcomes for diabetics. [15][16][17][18][19][20][21][22] We have demonstrated with first generation materials that the PAD approach works invivo, showing insulin release from the injected depot only after an external LED light source transcutaneously stimulates the material. 23 Furthermore we have shown we can deliver sufficient insulin in this manner to effect a robust reduction in blood glucose.…”

Section: Introductionmentioning

confidence: 99%

Hydrophobic Tags for Highly Efficient Light-Activated Protein Release

2019

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We have previously described the Photoactivated Depot (PAD) approach for the light stimulated release of therapeutic proteins such as insulin. The aim of this method is to release of insulin from a shallow dermal depot in response to blood glucose information, using transcutaneous irradiation. Our first approach utilized a photocleavable group that linked insulin to an insoluble but injectable polymer bead. The bead conferred insolubility, insuring that the injected material stayed at the site of injection, until light cleaved the link, and allowed insulin to be absorbed systemically. While this proved to be effective, the use of a polymer to insure insolubility introduces two major design problems: 1) Low concentration of insulin, as a majority of the material is comprised of polymer, 2) Upon release of the insulin, the polymer has to be cleared from the system. To address these two problems, in this work we have pursued 'hydrophobic tags', photocleavable small non-polar molecules that confer insolubility to the modified insulin prior to irradiation without the bulk or need for biodegradation required of polymers. We developed a combined solid and solution phase synthetic approach that allowed us to incorporate a range of small non-polar moieties, including peptides, into the final depot materials. The resulting materials are >90% w/w insulin and have sharply decreased solubilities relative to unmodified insulin (≤1000x lower). We demonstrated that they can be milled into low micron sized particles that can be readily injected through a 31G needle. These suspensions can be prepared at an effective concentration of 20mM insulin, a concentration at which 120μl contains seven days of insulin for a typical adult. Finally, upon photolysis, the insoluble particles release soluble, native insulin in a predictable fashion. These combined properties make these new modified insulins nearly ideal as candidates for PAD materials.

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Future prospect of insulin inhalation for diabetic patients: The case of Afrezza versus Exubera

Cited by 54 publications

References 64 publications

The Role of Inhaled Insulin in the Management of Type 2 Diabetes

The Role of Inhaled Insulin in the Management of Type 2 Diabetes

Dynamic Rule-Based Algorithm to Tune Insulin-on-Board Constraints for a Hybrid Artificial Pancreas System

Hydrophobic Tags for Highly Efficient Light-Activated Protein Release

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