title: Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents.
abstract: 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).
  
  
  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.
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX juliorosenstock@dallasdiabetes.com.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: CPCLIN Clinical Research Center, São Paulo, Brazil.
authors.forename: Denise
authors.initials: D
authors.lastname: Franco
authors.affiliation: V.P. Komissarenko Institute of Endocrinology and Metabolism of AMS of Ukraine, Kiev, Ukraine.
authors.forename: Vadym
authors.initials: V
authors.lastname: Korpachev
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY.
authors.forename: Brad
authors.initials: B
authors.lastname: Shumel
authors.affiliation: MannKind Corporation, Paramus, NJ.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Ma
authors.affiliation: MannKind Corporation, Paramus, NJ.
authors.forename: Robert
authors.initials: R
authors.lastname: Baughman
authors.affiliation: MannKind Corporation, Paramus, NJ.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Amin
authors.affiliation: Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO.
authors.forename: Janet B
authors.initials: JB
authors.lastname: McGill
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D061386:Insulin, Regular, Human / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008863:Microspheres; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D011208:Powders / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061386:Insulin, Regular, Human; D008687:Metformin; D010919:Placebos; D011208:Powders