Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof-of-concept study.
OBJECTIVE
This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes.


METHODS
Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 +/- 6.6 years, body mass index 32.7 +/- 4.2 kg/m(2), glycosylated haemoglobin (HbA1c) 8.4 +/- 0.8% (mean +/- s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets.


RESULTS
INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (-2.7 vs. -3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (-1.23 vs. -1.05%), body weight (-1.9 vs. -2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (-1.15 micromol/l; p < 0.001) but not with GLA [-0.52 micromol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation.


CONCLUSIONS
In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies.
Hausmann
M
M
Profil Institut für Stoffwechselforschung GmbH, Hellersbergstr. 9, Neuss, Germany.
Dellweg
S
S
Osborn
C
C
Heinemann
L
L
Buchwald
A
A
Rosskamp
R
R
Genova
P
P
Heise
T
T
D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000627:therapeutic use; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D017211:Treatment Failure
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D013453:Sulfonylurea Compounds; D000069036:Insulin Glargine; D008687:Metformin