Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents.

Objective: To investigate the efficacy and safety of prandial Technosphere inhaled insulin (TI), an inhaled insulin with a distinct time action profile, in insulin-naïve type 2 diabetes (T2D) inadequately controlled on oral antidiabetes agents (OADs).

Research Design And Methods: Subjects with T2D with HbA1c levels ≥7.5% (58.5 mmol/mol) and ≤10.0% (86.0 mmol/mol) on metformin alone or two or more OADs were randomized to add-on prandial TI (n = 177) or prandial Technosphere inhaled placebo (TP) (n = 176) to their OAD regimen in this double-blind, placebo-controlled trial. Primary end point was change in HbA1c at 24 weeks.

Results: TI significantly reduced HbA1c by -0.8% (-9.0 mmol/mol) from a baseline of 8.3% (66.8 mmol/mol) compared with TP -0.4% (-4.6 mmol/mol) (treatment difference -0.4% [95% CI -0.57, -0.23]; P < 0.0001). More TI-treated subjects achieved an HbA1c ≤7.0% (53.0 mmol/mol) (38% vs. 19%; P = 0.0005). Mean fasting plasma glucose was similarly reduced in both groups. Postprandial hyperglycemia, based on 7-point glucose profiles, was effectively controlled by TI. Mean weight change was 0.5 kg for TI and -1.1 kg for the TP group (P < 0.0001). Mild, transient dry cough was the most common adverse event, occurring similarly in both groups (TI, 23.7%; TP, 19.9%) and led to discontinuation in only 1.1% of TI-treated and 3.4% of TP-treated subjects. There was a small decline in forced expiratory volume in 1 s in both groups, with a slightly larger decline in the group receiving TI (TI, -0.13 L; TP, -0.04 L). The difference resolved after treatment discontinuation.

Conclusions: 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.