INHALE-3 Analysis Supports Need for Increased Technosphere Insulin Doses, With Roy Beck, MD, PhD

Technosphere insulin (TI), an ultrarapid-acting inhaled insulin, has shown its efficacy in glucose management in higher doses than have been approved for adults with type 1 diabetes (T1D), according to an analysis from INHALE-3.1

“One of the challenges that we have in treating patients with injectable insulin is that it’s injected underneath the skin,” Roy Beck, MD, PhD, founder of the Jaeb Center for Health Research, told HCPLive in an exclusive interview. “It takes some time to be absorbed into the bloodstream, and so there’s a delay much greater than what we see with a pancreas producing insulin normally. When insulin is inhaled and goes into the lung, it distributes into the bloodstream very rapidly and becomes something very close to endogenous insulin.”

TI is the first and only ultrarapid-acting inhaled insulin to receive approval from the US Food and Drug Administration (FDA) for the improvement of glycemic control in patients with diabetes mellitus. Initially approved under the brand name Afrezza, TI received an update to its prescribing information on January 26, 2026, revising the recommendations for starting mealtime dosage when patients switch from subcutaneous mealtime insulin regimens.2

INHALE-3 was a multicenter, randomized, controlled study comparing the safety and efficacy of TI combined with insulin degludec versus standard care in adults with T1D. This latter group included treatment regimens of multiple daily injections or insulin pump therapy, including automated insulin delivery (AID) systems. Patients were not blinded to treatment.1

Upon randomization, patients in the TI treatment arm transitioned from their previous insulin therapy using a conversion ratio modified from existing recommendations, wherein the TI dose is calculated by multiplying the patient’s usual subcutaneous rapid-acting insulin analogue (RAA) dose by 2 and rounding down to the nearest available cartridge size from among 4, 8, or 12 U, or a combination thereof. The first dose of TI was administered in-clinic, after which patients were instructed to titrate their TI dose over time based on glucose response.1

The present analysis analyzed a specific subgroup of patients who had been randomized to the T1D and degludec arm and had complete insulin dosing data at all 3 key timepoints – baseline, week 17, and week 30. Patients were eligible for inclusion if they had non-missing data for total daily insulin doses and mealtime dosing at each time point. A total of 35 patients from INHALE-3 met these criteria and were included.1

Among these patients, the mean age was 46 years with a baseline A1c of 7.72% (standard deviation [SD] +/- 1; 61 mmol/mol). Prior to TI initiation, 40% of participants were using AID. The mean baseline bolus and basal dose of RAA insulin were 23.9 U/d, with a bolus/basal ratio of roughly 50%/50%. After 30 weeks of monitoring, mean total daily TI dose increased from 36 U at baseline to 48 U at 17 weeks (P = .002) and 52 U at 30 weeks (P <.001). By 30 weeks, the TI bolus/basal ratio had also shifted to around 70%/30% (P <.001). At 17 weeks, 57% of participants had increased their TI dose by >4 U, which then increased to 74% at 30 weeks. Notably, investigators recorded no new safety signals with TI treatment.1

Given these data, the FDA’s approval of higher starting doses for TI is no surprise. Investigators did, however, emphasize that higher overall dosing requirements are needed to support individualized titration and help patients reach their glycemic goals.1

“All patients could potentially improve with this, because everyone who has diabetes has the potential for a spike after they eat,” Beck said. “There’s a real benefit to trying to reduce that by getting insulin into the bloodstream faster, although the effect of that insulin goes away pretty quickly. There were a substantial proportion of participants who improved quite a bit, but there were some who didn’t, and I think it’s largely because it took a certain regimented approach to frequent inhaling if your glucose was still high.”

Editors’ Note: Beck reports that his institution has received funding on his behalf from Insulet, Tandem Diabetes Care, Beta Bionics, Abbott, Dexcom, Sequel Med Tech, and others.

References

1. Rittenberry J, Sylvan J, Mycue L-E, Griparic L, Kaiserman K. Inhaled insulin dosing in a randomized trial in adults with type 1 diabetes. AACE Endocrinology and Diabetes. Published online February 5, 2026. doi:10.1016/j.aed.2025.12.020

2. MannKind Corporation. MannKind Announces FDA Approval of Updated Afrezza Label Providing Starting Dose Guidance when Switching from Multiple Daily Injections (MDI) or Insulin Pump Mealtime Therapy. January 26, 2026. Accessed April 17, 2026. https://investors.mannkindcorp.com/news-releases/news-release-details/mannkind-announces-fda-approval-updated-afrezzar-label-providing