ADA 2026: Optimized Inhaled Insulin Dosing Outperforms Subcutaneous Analogs for Postprandial Glucose in T1D

Managing postprandial hyperglycemia remains one of the most persistent challenges in type 1 diabetes (T1D) care. New data presented at the 2026 American Diabetes Association (ADA) Scientific Sessions in New Orleans, Louisiana, suggest that individualized, weight-based titration of Technosphere inhaled insulin (TI; Afrezza, MannKind Corporation) may offer a meaningful advantage over subcutaneous rapid-acting analog (RAA) insulin in reducing postmeal glucose excursions, but only when patients are dosed at appropriately higher levels.¹

Poster Findings: Dose Matters

The researchers analyzed data from adults with T1D who were enrolled in the INHALE-3 (NCT05904743) trial. Participants randomized to TI completed 2 standardized 120-minute meal challenges: one using a dose converted from their prior RAA regimen, and a second after 17 weeks of individualized titration. Participants in the usual care (UC) arm completed the same meal challenge using their existing RAA regimen.¹

Doses were stratified as high or low based on median weight-based dosing (units per kilogram, U/kg) within each group. Mean glucose excursion was significantly lower in the TI-high group compared with the UC-high group from 30 to 120 minutes postmeal (P < .05). TI-high also demonstrated lower excursion than TI-low (P < .05). No significant difference was observed between UC-low and UC-high, nor between TI-low and UC-low. Mean U/kg values were about 0.074 for TI-low, 0.16 for TI-high, 0.042 for UC-low, and 0.084 for UC-high.¹

Background: TI's Pharmacokinetic Advantage

Faster absorption and clearance of TI lead to a faster onset, shorter duration of action, and rapid suppression of endogenous glucose production, making it theoretically more effective in meeting prandial insulin needs. TI is characterized by a "rapid on, rapid off" glucose-lowering action profile that closely mimics endogenous insulin secretion. Action peaks after approximately 40 to 60 minutes and lasts for 2 to 3 hours. Compared with insulin aspart, TI is associated with a lower risk of late postprandial hypoglycemia and weight gain.^2,3

Despite these advantages, TI has historically been underutilized. Although TI was approved by the FDA a decade ago, it is not frequently prescribed despite its potential benefits. The INHALE-3 trial, from which this poster's data is drawn, was designed to more rigorously evaluate TI's real-world potential.⁴

INHALE-3 Trial Context

In total, 123 adults with T1D participated in a 17-week multicenter randomized controlled trial comparing a regimen of TI plus insulin degludec versus usual care, which consisted predominantly of automated insulin delivery (AID) or multiple daily insulin injections. Approximately 30% of individuals with T1D who took TI plus basal insulin reached a hemoglobin A_1c of less than 7% at 17 weeks, compared with 17% in the usual care group. The new ADA 2026 poster extends this work by examining whether U/kg dosing strata can help identify which patients are most likely to benefit from TI therapy.^4,5

The poster's authors concluded that 17 weeks of titration resulted in higher individualized U/kg dosing and that under-dosing TI yielded outcomes comparable to standard therapy, while higher-dose TI produced significantly improved postprandial excursions. This suggests that some patients with T1D may require meaningfully higher weight-based doses for optimal meal coverage.¹

Implications for Clinical Practice and Pharmacy

Afrezza is delivered as a dry powder through a small breath-activated inhaler with an onset of action of about 12 minutes, and inhaled insulin is now included in the 2026 ADA Standards of Care treatment landscape. Its inclusion signals growing recognition of TI as a viable prandial option and raises the stakes for pharmacists who counsel patients starting or titrating this therapy.^1,6

Practical aspects of Afrezza use include appropriate patient selection, as well as the importance of patient education and counseling for optimal outcomes. Pharmacists are well-positioned to support both. Community pharmacists are able to provide greater access to care by dispensing medications, providing education, and supporting chronic disease management through team-based care. For patients beginning TI, counseling on inhaler technique, the need for spirometry screening prior to initiation, and the importance of not smoking are all areas where pharmacist engagement can directly affect patient safety and outcomes.⁷

As data from INHALE-3 and its substudies continue to mature, the findings underscore a critical message for pharmacy practice: TI's full potential is likely realized only through individualized titration. Understanding the dose-response relationship, and communicating it effectively to patients, will be essential to ensuring that those who could benefit most from inhaled insulin actually do.

REFERENCES

1. Rittenberry JT, Sylvan J, Mycue LE, Rinker JK, Nguyen J, Kaiserman K. Inhaled insulin demonstrates lower variability and faster onset compared with subcutaneous rapid-acting analogs. Poster presented at: 2026 American Diabetes Association Scientific Sessions; June 5-8, 2026; New Orleans, Louisiana. Accessed via the Online ADA 2026 Platform.

2. Hirsch IB, Blevins TC, Valent AM, Riddell MC. Case reports: practical use of pulmonary inhaled (Technosphere) insulin in type 1 diabetes, type 2 diabetes, and pregnancy. Diabetes Technol Ther. 2026;28(1_suppl):55S-63S. doi:10.1177/15209156251412813

3. Rosenstock J, Lorber DL, Gnudi L, et al. Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomised trial. Lancet. 2010;375(9733):2244-2253. doi:10.1016/S0140-6736(10)60632-0

4. Hirsch IB, Beck RW, Marak MC, et al. A randomized trial comparing inhaled insulin plus basal insulin versus usual care in adults with type 1 diabetes. Diabetes Care. 2025;48(3):353-360. doi:10.2337/dc24-1832

5. Gallagher A. INHALE-3 study data shows diabetes care is not "one-size-fits-all." Pharmacy Times. Published July 4, 2024. Accessed June 4, 2026. https://www.pharmacytimes.com/view/inhale-3-study-data-shows-diabetes-care-is-not-one-size-fits-all-

6. MannKind Corporation—Afrezza (insulin human) inhalation powder: Full Prescribing information. MannKind Corporation. Accessed June 4, 2026. https://afrezza.com/pdf/Full-Prescribing-Information-Feb-2023-1

7. Orabone AW, Do V, Cohen E. Pharmacist-managed diabetes programs: improving treatment adherence and patient outcomes. Diabetes Metab Syndr Obes. 2022;15:1911-1923. doi:10.2147/DMSO.S342936