Initiation of prandial insulin therapy with AIR inhaled insulin or insulin lispro in patients with type 2 diabetes: A randomized noninferiority trial.
BACKGROUND
Insulin initiation in patients with type 2 diabetes is often delayed because of concerns about injections. Our objective was to compare the effects of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) with those of injectable insulin on glycemic control and safety.


METHODS
This was planned as a 24-month, open-label, randomized study in adults with diabetes inadequately controlled by one or more oral antihyperglycemic medications (OAMs). Following a 2-week baseline period, patients continued OAMs and were randomized to AIR insulin (n = 208) or insulin lispro (n = 203) before meals. The primary end point was hemoglobin A1C (A1C) change from baseline to 6 months. Noninferiority was established if the upper limit of the 95% confidence interval of the difference in A1C change was < or =0.4%.


RESULTS
Early termination of the study diminished the number of patients for the 12- and 24-month analyses, but not for the primary 6-month end point analyses. AIR insulin and injectable insulin groups had comparable baseline A1C values (8.18% vs. 8.21%, respectively). Change in A1C from baseline to 6-month end point was similar (least squares mean, -0.81 +/- 0.09% and -0.87 +/- 0.09%; 95% confidence interval for the difference -0.117, 0.234; P = 0.51) and so were final A1C values of 7.36% and 7.31% for AIR insulin and injectable insulin, respectively. At 6 months, no differences were observed in eight-point profiles, overall and nocturnal hypoglycemia, and weight gain. Greater decreases in spirometry were observed in the AIR insulin group at 12 months. Cough was the most frequently reported adverse event (20% [AIR insulin] vs. 10% [insulin lispro]; P = 0.002).


CONCLUSIONS
Treatment with AIR insulin resulted in similar improvement in glycemic control compared with insulin lispro. More frequent cough and greater decrease in spirometry were observed with AIR insulin.
Gross
Jorge L
JL
Centro de Pesquisas em Diabetes, Porto Alegre, Brazil.
Nakano
Masako
M
Colon-Vega
Gildred
G
Ortiz-Carasquillo
Ramon
R
Ferguson
Jeffrey A
JA
Althouse
Sandra
S
Tobian
Janet A
JA
Berclaz
Pierre-Yves
PY
Milicevic
Zvonko
Z
D000280:Administration, Inhalation; D000368:Aged; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D061268:Insulin Lispro; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D018579:Patient Selection; D014797:Vital Capacity / Q000187:drug effects
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D008687:Metformin