Improved Postprandial Glucose with Inhaled Technosphere Insulin Compared with Insulin Aspart in Patients with Type 1 Diabetes on Multiple Daily Injections: The STAT Study
Journal of Diabetes Science and Technology (Ahead of Print)
Background: The majority of therapies have generally targeted fasting glucose control, and current mealtime insulin therapies have longer time action profiles than that of endogenously secreted insulin. The primary purpose of this study was to assess both glucose time-in-range (TIR: 70–180 mg/dL) and postprandial glucose excursions (PPGE) in 1–4 h using a real-time continuous glucose monitor (CGM) with Technosphere insulin (TI) versus insulin aspart in patients with type 1 diabetes (T1DM) on multiple daily injections (MDI).
Research Design and Methods: This pilot, investigator-led, collaborative, open-label, multicenter, clinical research trial enrolled 60 patients with T1DM with HbA1c levels ≥6.5% and ≤10%. Individuals were randomized to treatment with titrated TI (n = 26) or titrated insulin aspart (n = 34), stratified by baseline HbA1c levels (≤8% or >8%). All were required to wear a real-time CGM throughout the trial. All patients in the TI group were advised to take supplemental inhalations at 1 and 2 h after meals if indicated based on postprandial glucose (PPG) values. The coprimary outcomes were assessed both in the full intent-to-treat population and in those individuals randomized to TI who were compliant with supplemental doses ≥90% of the time (n = 15). The CGM data were analyzed using linear regression models.
Results: Overall, those treated with TI versus aspart achieved comparable TIR, but less time spent in hypoglycemia (<60 and <50 mg/dL, both P < 0.05). In the TI-compliant group (n = 15), TIR was significantly greater (62.5% ± 2.6% vs. 53.8% ± 1.7%, P = 0.009) and time in hyperglycemia >180 mg/dL was lower (34.2% ± 2.7% vs. 41.0% ± 1.7%, P = 0.045) as compared with the aspart group. PPG was also significantly lower in the TI cohort at 60 and 90 min postmeal, and PPGE were lower in the TI-compliant group as compared with the aspart group over 1–4-h postmeal (P < 0.05). In addition, there was weight gain in the aspart group compared with weight loss in the TI group (P = 0.006) despite higher prandial TI insulin dose.
Conclusions: We conclude that using TI appropriately at mealtimes with supplemental dosing improves prandial glucose (TIR and 1–4 h) control without any increase in time in hypoglycemia or weight gain in patients with T1DM on MDI. The study results support a larger study using a treat-to-target design to confirm these findings.
The Need for Faster Insulin: Problem Solved?
A Population Dose–Response Model for Inhaled Technosphere Insulin Administered to Healthy Subjects
—Published June 1, 2021 / onlinelibrary.wiley.com
Technosphere insulin (TI), an inhaled insulin with a fast onset of action, provides a novel option for the control of prandial glucose. A euglycemic glucose clamp study was performed to compare the effects of TI and regular human insulin (RHI) on the induced glucose infusion rate (GIR) in healthy volunteers. Generation of a dose–response relationship between insulin dose and effect (expressed as AUC of GIR) was not possible from the clinical data directly. The GIR recording time was too short to capture the full effect and higher doses were not tested. Thus, a pharmacokinetic-GIR model was developed to simulate GIR for a sufficient time window of 20 h and for higher doses. A dose–response model was then generated from the simulated GIR profiles. The resulting model provides an ED50 for TI that is 5-fold higher than for RHI, a ratio that can be used as conversion factor for equivalent doses of RHI and TI.
— texasreader (@livenlearn2015) May 2, 2021
Pharmacokinetic and Pharmacodynamic
Properties of a Novel Inhaled Insulin
Journal of Diabetes Science and Technology
2017, Vol. 11(1) 148–156
Advances in insulin treatment options over recent decades have markedly improved the management of diabetes. Despite this, glycemic control remains suboptimal in many people with diabetes. Although postprandial glucose control has been improved with the development of subcutaneously injected rapid-acting insulin analogs, currently available insulins are not able to fully mimic the physiological time–action profile of endogenously secreted insulin after a meal. The delayed onset of metabolic action and prolonged period of effect induce the risk of postprandial hyperglycemia and late postprandial hypoglycemia. A number of alternative routes of insulin administration have been investigated over time in an attempt to overcome the limitations associated with subcutaneous administration and to provide an improved time–action insulin profile more closely simulating physiological prandial insulin release. Among these, pulmonary insulin delivery has shown the most promise. Technosphere® Inhaled Insulin (TI) is a rapid-acting inhaled human insulin recently approved by the FDA for
prandial insulin therapy. In this article we discuss the pharmacokinetic and pharmacodynamic properties of TI, and, based on key studies performed during its clinical development, the implications for improved postprandial glucose control.
— AJMC-Diabetes Mgt (@EBDiabetes) September 18, 2020
Patients Report Barriers to Getting Afrezza, but A1C Results Are Worth It
Published Online: September 16, 2020 on ajmc.com/
— AJMC-Diabetes Mgt (@EBDiabetes) September 16, 2020
Making Insulin Accessible: Does Inhaled Insulin Fill an Unmet Need?
McGill JB, Ahn D, Edelman SV, Kilpatrick CR, Santos Cavaiola T.
Adv Ther. 2016 Jul 6. [Epub ahead of print]
Glycemic control is fundamental to the management of diabetes. However, studies suggest that a significant proportion of people with diabetes, particularly those using insulin, are not achieving glycemic targets. The reasons for this are likely to be multifactorial. The real and perceived risk of hypoglycemia and the need for multiple daily injections are widely recognized as key barriers to effective insulin therapy. Therefore, there is a clear unmet need for a treatment option which can help mitigate these barriers. Alternative methods of insulin administration have been under investigation for several years, and pulmonary delivery has shown the most promise to date. Inhaled Technosphere® Insulin (TI; Afrezza®; MannKind Corporation) was approved in 2014 for use as prandial insulin in people with diabetes. TI shows a more rapid onset of action and a significantly faster decline in activity than current subcutaneous rapid-acting insulin analogs (RAAs), and TI is more synchronized to the physiologic timing of the postprandial glucose excursion. This results in lower postprandial hypoglycemia with similar glycemic control compared with RAAs, and less weight gain. Together with the ease of use of the TI inhaler and the reduction in the number of daily injections, these findings imply that TI may be useful in helping to overcome patient resistance to insulin, improve adherence and mitigate clinical inertia in health-care providers, with potential beneficial effects on glycemic control.
— Medic one (@alpha2282) June 27, 2021
— MannKind Corporation (@MannKindCorp) June 22, 2021
The Role of Inhaled Insulin in the
Management of Type 2 Diabetes
Wesley Nuffer, Jennifer Trujillo
Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy & Pharmaceutical
Sciences, Aurora, CO, USA
Received 17 March 2016; accepted 18 April 2016; published 21 April 2021
(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.)
Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm – 2016 Executive Summary
Volume 22, Issue 1 (January 2016)
(Patients whose glycemia remains uncontrolled while receiving basal insulin and those with symptomatic hyperglycemia may require combined basal and mealtime bolus insulin. Rapid-acting analogs (lispro, aspart, or glulisine) or inhaled insulin are preferred over regular human insulin because the former have a more rapid onset and offset of action and are associated with less hypoglycemia (137). The simplest approach is to cover the largest meal with a prandial injection of a rapid-acting insulin analog or inhaled insulin and then add additional mealtime insulin later, if needed. Several randomized controlled trials have shown that the stepwise addition of prandial insulin to basal insulin is safe and effective in achieving target A1C with a low rate of hypoglycemia (138–140). A full basal-bolus program is the most effective insulin regimen and provides greater flexibility for patients with variable mealtimes and meal carbohydrate content (140).)
Afrezza Inhaled Insulin: The
Fastest-Acting FDA-Approved Insulin on
the Market Has Favorable Properties
Journal of Diabetes Science and Technology 2014, Vol. 8(6) 1071–1073
(Afrezza will fill a needed role for patients who do not wish to
dose themselves for prandial insulin coverage with insulin
from a needle injection. The rapid onset and offset of this
insulin may well prove to be a great advantage in minimizing
glucose fluctuations without much of the risk of late postinjection
hypoglycemia. Now that MannKind signed a marketing
agreement with the world’s largest insulin company,
Sanofi, it is likely that Afrezza will soon be made available
in many countries by way of a well-established distribution
system. I look forward to seeing Afrezza used for mealtime
insulin therapy in a closed-loop system and for many other
situations where bolus insulin therapy is needed but late
postprandial hypoglycemia is intolerable.)
Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents
Diabetes Care December 2015 vol. 38 no. 12 2274-2281
(Prandial TI added to one or more OADs in inadequately controlled T2D is an effective treatment option. Mild, transient dry cough was the most common adverse event.)
Inhaled Technosphere Insulin Compared With Injected Prandial Insulin in Type 1 Diabetes: A Randomized 24-Week Trial
Diabetes Care December 2015 vol. 38 no. 12 2266-2273
(In patients with type 1 diabetes receiving basal insulin, HbA1c reduction with TI was noninferior to that of aspart, with less hypoglycemia and less weight gain but increased incidence of cough.)
Technosphere Inhaled Insulin: Is
Diabetes Care Volume 38, December 2015
(In summary, the ultrafast profile of inhaled Technosphere insulin is novel and brings several possibilities. Of particular interest is intensive mealtime insulin coverage with less hypoglycemia through
repeat doses or if used with injected prandial insulin. However, these possibilities are more speculative than proven. As such, inhaled insulin is still a convenience product rather than a proven advance in insulin therapy. However, it is at the forefront of several faster insulins that are in development . And the question remains-is faster better?)
Afrezza (Insulin Human) Inhalation Powder
A New Inhaled Insulin for the Management Of Type-1 or Type-2 Diabetes Mellitus
P T. 2015;40(11): 735-741
(A comprehensive review of Afrezza, covering the pharmacology, pharmacokinetics, clinical trials, safety profile, warnings and precautions, dosage and administration, use in special populations, drug-drug interactions, availability and costs of Afrezza.
Conclusion is that Afrezza is a new dry powder/inhaler system for the delivery of Technosphere insulin to patients with T1DM or T2DM. It provides a promising, noninvasive alternative to SC insulin analogs to patients with T1DM or T2DM.)
Inhaled Insulin: Controlling A1C Without a Needle
Jennifer LaPreze, PharmD and Andrea Locklear, MS, PharmD, BCPS
US Pharm. 2015;40(10)(Diabetes suppl):3-7.
(Inhaled insulin may offer a therapy option to patients who have never considered taking mealtime insulin for various reasons. The inhaled option may change the perception of and fear associated with insulin therapy, as it does remove the need for injection and is a smaller device. It is imperative that patients receive education at the prescriber level and dispensing site to ensure that the medication is administered correctly and adverse events are avoided.)
Inhaled insulin therapy reduces HbA1c in poorly controlled type 2 diabetes
Rosenstock J, et al. Diabetes Care. 2015; doi:10.2337/dc15-0629. Endocrine Today, September 2015
Insulin Inhalation Therapy Effective in Treatment of Type 2 Diabetes
Published on specialtypharmacytimes.com on 2 September 2015
(Adding Afrezza insulin inhalation powder to oral diabetes medications significantly reduces HbA1C in adults with poorly controlled type 2 diabetes.)
Efficacy, safety, and patient acceptability of Technosphere inhaled insulin for people with diabetes: a systematic review and meta-analysis
Published Online on thelancet.com on 01 September 2021
(Glycaemic efficacy of Technosphere inhaled insulin is lower than that of subcutaneous insulin, but inhaled insulin has a lower risk of severe hypoglycaemia and weight gain. Long-term outcomes and safety with Technosphere insulin should be further investigated. Until further data for safety become available, Technosphere inhaled insulin should be reserved for healthy adults with diabetes who do not have pulmonary disease and who would otherwise delay initiating or intensifying insulin therapy because they are unwilling or unable to use injectable insulin.)
Afrezza Lowers HbA1C in Uncontrolled Type 2 Diabetes
Publishded on pharmacytimes.com on 31 August 2021
(Adding Afrezza insulin inhalation powder to oral diabetes medications significantly reduces HbA1C in adults with poorly controlled type 2 diabetes. )
Satisfaction and Quality of Life With Premeal Inhaled Versus Injected Insulin in Adolescents and Adults With Type 1 Diabetes
Published on care.diabetesjournals.org
(Treatment satisfaction was substantially more favorable, adherence barriers moderately lower, and quality of life moderately higher for inhaled compared with subcutaneous regimen. It remains to be demonstrated whether these patient-reported outcomes will translate into improved adherence and glycemic control.)
Adding Inhaled Insulin to Oral Meds
Published on ClinicalEndocrinologyNews.com on August 21, 2015
(Clinicians should consider adding prandial inhaled insulin to oral antidiabetic medication in those whose type 2 diabetes is not well controlled, according to a randomized trial of 353 patients.)
Inhaled insulin therapy reduces HbA1c in poorly controlled type 2 diabetes
Rosenstock J, et al. Diabetes Care. 2015; doi:10.2337/dc15-0629. August 12, 2015
(Adults with type 2 diabetes that is not well controlled on oral antidiabetes medications experienced a significant drop in HbA1c after adding Afrezza inhaled insulin to their regimen, according to research in Diabetes Care.)
Inhaled insulin: A “puff” than a “shot” before meals
Journal of Pharmacology and Pharmacotherapeutics | Published by Wolters Kluwer
Year : 2015 | Volume : 6 | Issue : 3 | Page : 126-129
A second-generation inhaled insulin for diabetes mellitus.
Am J Health Syst Pharm. 2015 Jul 15
Afrezza: An inhaled approach to insulin delivery.
J Am Assoc Nurse Pract. 2015 Mar 12.
Technosphere insulin (Afrezza): a new, inhaled prandial insulin.
Ann Pharmacother. 2015 Jan;49(1):99-106.
Afrezza Inhaled Insulin
The Fastest-Acting FDA-Approved Insulin on the Market Has Favorable Properties
David C. Klonoff, MD
J Diabetes Sci Technol November 2014 vol. 8 no. 6 1071-1073
(Afrezza will fill a needed role for patients who do not wish to dose themselves for prandial insulin coverage with insulin from a needle injection. The rapid onset and offset of this insulin may well prove to be a great advantage in minimizing glucose fluctuations without much of the risk of late postinjection hypoglycemia. I look forward to seeing Afrezza used for mealtime insulin therapy in a closed-loop system and for many other situations where bolus insulin therapy is needed but late postprandial hypoglycemia is intolerable.)