Afrezza (recombinant human insulin inhalation) / MannKind - LARVOL DELTA

INHALE-1st: Afrezza® For Youth With Newly-Diagnosed Type 1 Diabetes (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Mannkind Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Inhaled Technosphere Insulin in Children with Diabetes: The INHALE-1 Extension Study. (PubMed, Diabetes Technol Ther) - "The INHALE-1 extension phase showed no safety concerns. Although HbA1c levels deteriorated slightly during the study, in view of the safety profile and increased patient satisfaction in the RCT portion of the trial, TI may be a useful treatment option for some pediatric patients with diabetes, particularly for those who choose not to or are unable to use an AID system."

Journal • Diabetes • Metabolic Disorders • Pediatrics • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Pulmonary Safety and Clinical Considerations for Inhaled Insulin: A Comprehensive Review. (PubMed, Diabetes Technol Ther) - "Ongoing innovation in inhaled insulin led to FDA approval of Technosphere® Insulin (TI), the therapeutic component of the Afrezza® inhaled insulin delivery system (MannKind Corporation, Westlake Village, CA). However, many clinicians remain cautious about the potential for adverse events with chronic use beyond the duration of closely monitored clinical trials. In this article, we address the pulmonary safety concerns that are often associated with TI and present evidence demonstrating the safety of TI in type 1 diabetes and type 2 diabetes populations."

Journal • Review • Cough • Diabetes • Metabolic Disorders • Respiratory Diseases • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Insulins for type 2 diabetes. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparison chart: Some available insulins for type 2 diabetes. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

30 Years of Developing Inhaled Insulin. (PubMed, Diabetes Technol Ther) - "Since the discovery of insulin in 1921, we have seen a constant stream of innovative insulin formulations designed to more closely mimic physiological insulin secretion in people with type 1 diabetes and insulin-requiring type 2 diabetes. This article briefly reviews the development of inhaled insulin over the past 30 years."

Journal • Review • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Use of Inhaled Insulin with Automated Insulin Delivery Systems. (PubMed, Diabetes Technol Ther) - "While the integration of inhaled insulin with AID systems presents an opportunity to address the limitations of subcutaneous insulin formulations, challenges remain in harmonizing the pharmacokinetics of inhaled insulin with AID systems. This article reviews the current evidence supporting the potential role of concomitant use of TI with AID and gaps in our current knowledge that need to be filled with future studies."

Journal • Review • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Impact of Inhaled Insulin Therapy on Hypoglycemia. (PubMed, Diabetes Technol Ther) - "Technosphere inhaled insulin is a viable option for mealtime insulin coverage and post-meal corrections, providing a "fast on, fast off" insulin activity profile that closely aligns with the timing of glucose absorption from meals to achieve desired postprandial glycemic control while likely minimizing the risk of hypoglycemia. This article discusses the advantages of TI over injected rapid-acting insulin analogs in addressing hypoglycemia fear and the other barriers associated with treatment adherence."

Journal • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Potential Role of Inhaled Insulin in the Management of Gestational Diabetes Mellitus and Pediatric Type 1 Diabetes. (PubMed, Diabetes Technol Ther) - "Technosphere® insulin (TI), the main component of the Afrezza® Inhalation System, has the potential to address these challenges by improving glycemic management, reducing hypoglycemia, and promoting treatment adherence. TI is characterized by a rapid onset of action and a short duration of effect, distinguishing it from traditional injectable rapid-acting insulin analogs. This article discusses greater flexibility in insulin delivery, along with potential applications, benefits, and challenges of treatment with Technosphere inhaled insulin in these two patient populations."

Journal • Review • Diabetes • Gestational Diabetes • Hypoglycemia • Metabolic Disorders • Pediatrics • Type 1 Diabetes Mellitus

Overcoming Therapeutic Inertia with Inhaled Insulin Therapy. (PubMed, Diabetes Technol Ther) - "Inhaled insulin therapy with Technosphere® insulin has the potential to overcome these obstacles. This article reviews the impact of therapeutic inertia in individuals with diabetes who are treated with insulin or require insulin therapy and discusses how the use of inhaled insulin may overcome many of the barriers to insulin treatment intensification."

Journal • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Potential Applications of Inhaled Insulin in Diabetic Ketoacidosis Prevention and During Exercise: Two Case Presentations. (PubMed, Diabetes Technol Ther) - "Unlike injected or infused rapid-acting insulins, Technosphere® insulin (TI) may bypass the slower absorption and hepatic degradation associated with subcutaneous delivery, ensuring faster systemic availability, however definitive studies have not been conducted...The RAA and URAA profile characteristics are also problematic for individuals who engage in regular physical activity, often resulting in hypoglycemia, hyperglycemia, or both. This article reviews the challenges and potential dangers associated with managing T1D and discusses how TI, the only commercially available inhaled insulin, may overcome the inherent limitations of current RAA and URAA therapies."

Journal • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Dosing Afrezza: It's Not that Complicated. (PubMed, Diabetes Technol Ther) - "Although Afrezza has been commercially available for more than a decade, its adoption has been limited by lack of clinician awareness, confusion about dosing, and skepticism about its efficacy and safety. This article presents our perspectives on Afrezza regarding dosing and titration strategies, patient selection and education, and other practical considerations."

Journal • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

The Potential of Inhaled Insulin Therapy in Overcoming Treatment Barriers in People with Insulin-Treated Diabetes. (PubMed, Diabetes Technol Ther) - "The Afrezza® inhaled insulin system, with Technosphere® insulin (TI), is a promising alternative to subcutaneous insulin injections, offering a rapid pharmacokinetic profile and ease of use...Individual choice, supported by shared decision-making, is essential for individualized diabetes care, empowering people with diabetes and improving outcomes. Broader adoption requires increased clinician awareness and insurance coverage."

Journal • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Pain

Case Reports: Practical Use of Pulmonary Inhaled (Technosphere) Insulin in Type 1 Diabetes, Type 2 Diabetes, and Pregnancy. (PubMed, Diabetes Technol Ther) - "Afrezza® with Technosphere® inhaled insulin (TI) offers a novel therapeutic option with a rapid pharmacokinetic and pharmacodynamic profile, addressing challenges associated with injectable insulin therapies. This article presents case reports that illustrate the clinical applications of TI across diverse patient populations, including type 1 diabetes, type 2 diabetes (T2D), pregnancy complicated by T2D, and exercise-related glycemic management."

Journal • Diabetes • Gestational Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Inhaled Insulin Decoded: Dispelling Myths and Presenting Clinical Evidence. (PubMed, Cureus) - "The review also discusses practical aspects of Afrezza® use, especially proper patient screening based on spirometry testing, patient education, and counseling. Ultimately, Afrezza® signifies a transformation in insulin therapy, offering an effective and convenient alternative to prandial insulin for adult patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM)."

Journal • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Mood Disorders • Psychiatry • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Real-World Incidence of Lung Malignancy and Chronic Obstructive Pulmonary Disease with Inhaled Insulin in People with Diabetes. (PubMed, Diabetes Technol Ther) - "No association was found between inhaled insulin and any lung malignancy. Inhaled insulin was associated with a threefold increase in COPD versus RAA although the absolute risk was low. The biological plausibility of this association is not definitive. Given the retrospective design and potential for ascertainment bias, causal inference is limited although findings underscore the need for continued evaluation of inhaled insulin's pulmonary safety."

Journal • Real-world evidence • Chronic Obstructive Pulmonary Disease • Diabetes • Immunology • Lung Cancer • Metabolic Disorders • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Type 2 Diabetes Mellitus

A Real-World Data Assessment of Pulmonary Toxicity of Inhaled Insulin for Diabetes. (PubMed, Diabetes Technol Ther) - "While there are limitations to the interpretation of results from a study using RWD, it is reassuring that there was no increase in pulmonary toxicity attributable to inhaled TI for treatment of diabetes with respect to lung cancer, COPD, emphysema, and chronic bronchitis."

Journal • Real-world evidence • Chronic Obstructive Pulmonary Disease • Diabetes • Immunology • Lung Cancer • Metabolic Disorders • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

INHALE-1: A Multicenter Randomized Trial of Inhaled Technosphere Insulin in Children With Type 1 Diabetes. (PubMed, Diabetes Care) - "The primary analysis did not meet the prespecified criteria for HbA1c noninferiority. However, TI use was safe over 26 weeks without affecting pulmonary function and was associated with greater treatment satisfaction and less weight gain compared with RAA, supporting TI as a treatment option for some pediatric patients with type 1 diabetes."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Pediatrics • Type 1 Diabetes Mellitus

Replacing or Supplementing Automated Insulin Delivery With Inhaled Insulin: A 90-Day Randomized Controlled Trial. (PubMed, J Diabetes Sci Technol) - "This proof-of-concept study demonstrated the safety and efficacy of TI, at a higher modified dose conversion, when added for mealtime control to an AID system or was used for glycemic control with basal insulin."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

INHALE-1st: Afrezza® For Youth With Newly-Diagnosed Type 1 Diabetes (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Mannkind Corporation

New P2 trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

MannKind Announces U.S. FDA Accepts for Review its Supplemental Biologics License Application (sBLA) for Inhaled Insulin (Afrezza) in Children and Adolescents Aged 4-17 Years Living with Diabetes (GlobeNewswire) - "The application has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of May 29, 2026...The sBLA is based on results from the Phase 3 INHALE-1 study in children and adolescents between the ages of 4-17 who are living with either type 1 or type 2 diabetes....The submission also included safety data from the study’s 26-week extension phase in which all remaining MDI patients switched to Afrezza. Full results will be shared at the International Society for Pediatric and Adolescent Diabetes (ISPAD) in early November."

FDA filing • P3 data • PDUFA • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

MannKind Completes Acquisition of scPharmaceuticals, Accelerating Revenue Growth in Cardiometabolic Care (Mannkind Corp Press Release) - "The transaction will strengthen MannKind’s commercial and medical capabilities by integrating scPharmaceuticals’ experienced team into its existing infrastructure. MannKind is positioned as a diversified, growth-focused biopharmaceutical company with its commercial assets—Afrezza, FUROSCIX and V-Go -- along with Tyvaso DPI-related revenues, contributing to an annualized run rate of over $370 million based on Q2 2025 results. Additionally, the FUROSCIX ReadyFlow Autoinjector supplemental New Drug Application (sNDA) filing was submitted as planned in Q3 2025."

M&A • Pulmonary Arterial Hypertension • Type 2 Diabetes Mellitus

Squamous Cell Carcinoma of the Lung in a Patient Using Inhaled Insulin: A Case Report and Review of Pulmonary Safety Concerns (ENDO 2025) - "Given these risks, clinicians should carefully consider alternative treatments for patients with lung disease or cancer risk factors, monitor pulmonary health regularly, and educate patients about potential symptoms. Further research is needed to establish a definitive causal relationship and understand the long-term safety of Afrezza."

Case report • Clinical • Review • Clear Cell Renal Cell Carcinoma • Cough • Diabetes • Genito-urinary Cancer • Lung Cancer • Metabolic Disorders • Oncology • Pain • Pulmonary Disease • Renal Cell Carcinoma • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma • Type 1 Diabetes Mellitus

Efficacy and Safety of Prandial Technosphere Inhaled Insulin (Afrezza) Compared with Placebo in Adult Individuals with T2DM—Results from a Phase III Clinical Trial from India (ADA 2025) - "TI(Afrezza®) demonstrated a significant reduction in HbA1c in individuals from India with T2DM with no significant differences in lung function observed compared to placebo group. This study reaffirms TI as an effective and safe treatment option for T2DM management."

Clinical • P3 data • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Patient-Reported Outcomes with Use of Inhaled Technosphere Insulin (TI) (ADA 2025) - "Introduction and Objective: The INHALE-3 randomized trial (N=123) demonstrated HbA1c levels with a regimen of TI plus insulin degludec were non-inferior compared with a usual-care control group (about half using AID and half MDI). Participants who had poorer glycemic control and greater dissatisfaction with diabetes and with their insulin regimen at baseline showed more improvement in glycemic control and PROs, perhaps reflecting a greater openness to trying a different insulin delivery regimen."

Clinical • Patient reported outcomes • Diabetes • Hypoglycemia • Metabolic Disorders