FDA Approves Updated Starting Dose Guidelines for Inhaled Insulin Powder (Afrezza)

The US Food and Drug Administration (FDA) has approved an updated label for insulin human (Afrezza) inhalation powder, which provides guidance for starting dosages when switching from multiple daily injections (MDI) or insulin pump mealtime therapy in patients with type 1 diabetes (T1D).1

Announced by parent company MannKind Corporation on January 26, 2026, this decision was supported in part by results from the phase 4 INHALE-3 trial, which highlighted improved postprandial glucose outcomes after converting to inhaled insulin using this conversion dose. During the trial, patients transitioning to inhaled insulin achieved HbA1c <7% at 30 weeks, representing a 100% increase from baseline.2

“We expect that this label update will help support healthcare providers by providing clearer starting dose guidance when transitioning patients to inhaled insulin from subcutaneous mealtime insulin – whether injections or insulin pumps,” Kevin Kaiserman, MD, senior vice president, Therapeutic Area Head, Diabetes at MannKind, said in a statement.1

The updated guidelines recommend beginning inhaled insulin at a dose of 4 units if the current subcutaneous mealtime insulin dosage is ≤3 units; similarly, a mealtime insulin dose of 4-5 units correlates to a starting inhaled insulin dose of 8 units; a mealtime insulin dose of 6-7 units correlates to inhaled insulin 12 units, and ≥8 units of mealtime insulin correlates to 16 units of inhaled insulin at the starting dosage.1

Afrezza is the first and only ultra-rapid-acting inhaled insulin to receive FDA approval for glycemic control improvement in patients with T1D. The insulin is administered at the start of meals via a portable inhaler and is rapidly absorbed through the lungs using MannKind’s proprietary Technosphere technology. Afrezza is contraindicated during hypoglycemia episodes and in patients with chronic lung disease.1

INHALE-3 was a 17-week, randomized controlled trial including a 13-week extension, conducted across 19 sites in the US. Patients were eligible for enrollment if they exhibited T1D and were using MDI, an automated insulin delivery system, or a pump without automation to either continue standard of care or to transition to a daily basal injection plus inhaled insulin. Patients beginning the trial on inhaled insulin received a higher initial conversion dose than the prior US label guidelines.2

A total of 141 patients were enrolled, and 123 were randomly assigned to either inhaled insulin (n = 62) or standard of care therapy (n = 61). By 17 weeks, 57 patients in the inhaled insulin arm and 58 in the standard of care arm remained in the trial. Investigators found that 30% of the inhaled insulin group achieved <7% HbA1c at 17 weeks versus 17% of the standard of care group. Additionally, 21% of the inhaled insulin group achieved A1c <7% if baseline was >7%, compared to 0% of the standard of care arm. 24% of the inhaled insulin arm and 13% of the standard of care arm achieved time in response above 70% with no increased hypoglycemia.3

The 13-week extension saw patients assigned to standard of care shifted to inhaled insulin until week 30. This phase began with 45 subjects from the inhaled insulin group and 49 from the standard of care group. Over these additional 13 weeks, HbA1c levels were sustained.4

“We believe this refinement to the label helps support appropriate initiation of therapy while reinforcing Afrezza’s established clinical profile,” Kaiserman said.1

References

1. 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 January 26, 2026. https://investors.mannkindcorp.com/news-releases/news-release-details/mannkind-announces-fda-approval-updated-afrezzar-label-providing

2. MannKind Corporation. More Adults With Type 1 Diabetes Achieved A1C Goal (<7%) After Switching From Multiple Daily Insulin Injections or Automated Pumps to Inhaled Insulin (Afrezza). September 30, 2024. Accessed January 26, 2026. https://investors.mannkindcorp.com/news-releases/news-release-details/more-adults-type-1-diabetes-achieved-a1c-goal

3. MannKind Corporation. INHALE-3 Study Reveals Positive Readout in Head-to-Head Comparison of Inhaled Insulin vs. Usual Care in T1D; New Data Presented at American Diabetes Association’s 84th Scientific Sessions. June 22, 2024. Accessed January 26, 2026. https://investors.mannkindcorp.com/news-releases/news-release-details/inhale-3-study-reveals-positive-readout-head-head-comparison?_gl=1*123tt6h*_ga*Nzg3MTkxNzQ0LjE3MTgxMTMyMTU.*_ga_4PG70PBDQW*MTcxOTI3NzgzNi4zNC4xLjE3MTkyNzc4NDAuNTYuMC4w

4. Beck RW, Bailey RJ, Klein KR, et al. Inhaled Technosphere Insulin Plus Insulin Degludec for Adults with Type 1 Diabetes: The INHALE-3 Extension Study. Diabetes Technol Ther. 2025;27(3):170-178. doi:10.1089/dia.2024.0582