A comparison between simplified and intensive dose-titration algorithms using AIR inhaled insulin for insulin-naive patients with type 2 diabetes in a randomized noninferiority trial.
BACKGROUND
Insulin initiation and optimization is a challenge for patients with type 2 diabetes. Our objective was to determine whether safety and efficacy of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) using a simplified regimen was noninferior to an intensive regimen.


METHODS
This was an open-label, randomized study in insulin-naive adults not optimally controlled by oral antihyperglycemic medications. Simplified titration included a 6 U per meal AIR insulin starting dose. Individual doses were adjusted at mealtime in 2-U increments from the previous day's four-point self-monitored blood glucose (SMBG) (total < or =6 U). Starting Air insulin doses for intensive titration were based on fasting blood glucose, gender, height, and weight. Patients conducted four-point SMBG daily for the study duration. Insulin doses were titrated based on the previous 3 days' mean SMBG (total < or =8 U).


RESULTS
End point hemoglobin A1C (A1C) was 7.07 +/- 0.09% and 6.87 +/- 0.09% for simplified (n = 178) and intensive (n = 180) algorithms, respectively. Noninferiority between algorithms was not established. The fasting blood glucose (least squares mean +/- standard error) values for the simplified (137.27 +/- 3.42 mg/dL) and intensive (133.13 +/- 3.42 mg/dL) algorithms were comparable. Safety profiles were comparable. The hypoglycemic rate at 4, 8, 12, and 24 weeks was higher in patients receiving intensive titration (all P < .0001). The nocturnal hypoglycemic rate for patients receiving intensive titration was higher than for those receiving simplified titration at 8 (P < 0.015) and 12 weeks (P < 0.001).


CONCLUSIONS
Noninferiority between the algorithms, as measured by A1C, was not demonstrated. This finding re-emphasizes the difficulty of identifying optimal, simplified insulin regimens for patients.
Mathieu
C
C
University Hospital Gasthuisberg of the Catholic University of Leuven, Belgium.
Cuddihy
R
R
Arakaki
R F
RF
Belin
R M
RM
Planquois
J-M
JM
Lyons
J N
JN
Heilmann
C R
CR
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D015992:Body Mass Index; 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; D007003:Hypoglycemia / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D045162:Thiazolidinediones / Q000627:therapeutic use; D014797:Vital Capacity / Q000187:drug effects
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione