Inhaled
Insulin Has No Adverse Effects Found After Two-Year
Study
Treatment with inhaled insulin (INH) is associated
with an increase in insulin antibodies, but continuing
studies indicate that the insulin antibodies are
not associated with increased hemoglobin A1c (HA1c),
increased need for insulin, hypoglycemia, or allergic
reactions.
These
findings were presented during the 12th Annual
Meeting & Clinical Congress of the American
Association of Clinical Endocrinologists, May
14-18.
To
access the impact of insulin antibodies (IABs)
in patients completing initial safety studies,
an uncontrolled extension study lasting up to
24 months was conducted using INH as the only
form of short-acting insulin. Participants included
661 type 1 and 298 type 2 diabetic patients, previously
treated with subcutaneous insulin, and 439 insulin
naïve type 2 patients who had failed oral
agent therapies.
A semi-quantitative
radioligand-binding assay was performed to measure
IABs at the beginning and end of the parent trial
and every six months in the extension study. Binding
levels present in normal human serum was subtracted
from total binding results. Randomly selected
samples reflecting a wide range of IAB levels
were analysed from the subjects.
The
results showed that INH-treated patients with
either type 1 or type 2 diabetes experienced a
rise in insulin antibody levels after being switched
from short-acting SC insulin to INH.
"Our
findings indicated that INH-associated IABs are
predominantly of the IgG class, consistent with
SC-associated IABs. No adverse clinical impact
has been identified due to insulin antibody responses
resulting from use of inhaled insulin," said
lead author S. Edwin Fineberg, M.D., a professor
of medicine at the University of Indiana School
of Medicine, Indianapolis, United States. "The
overall patterns of antibody responses are consistent
with published SC insulin experience, he said.
Antibody
levels in the INH-treatment arms were higher,
relative to the control arms in which SC insulin
regimens were maintained. Paediatric subjects
with type 1 diabetes appeared to have higher baseline
and end-of-study mean antibody levels compared
to the pooled type 1 cohort (approximately 60%
over 18 years of age). Patients with type 1 diabetes
had higher baseline and end-of-study mean antibody
levels (over 30% but under 35%, according to bar
chart) than those with type 2 diabetes. The lowest
levels of antibodies were detected in type 2 insulin-naïve
patients who received INH in addition to oral
antihyperglycemic agent therapy. The majority
[92%] of those patients had insulin antibody percent
binding levels that were less then 10%.
Data
from the long-term extension trial shows that
mean and median antibody levels peak at 12 to
18 months of exposure, continued Dr. Fineberg.
"The
important thing to realize is that scatter plot
and regression analyses suggest that insulin antibodies
are not associated with increased HbA1c, short-
or long-acting insulin doses, or hypoglycemia
rates (overall or severe)," he said.
He
and his colleagues pointed out that there were
"no consistent associations" with fasting
plasma glucose, or in the lung studies of forced
expiratory volume during one second (FEV1) and
carbon monoxide diffusing capacity tests. In addition,
the pooled INH group did not have a higher incidence
of allergic-type adverse events than the comparison
groups, according to study data.
"Our
conclusion is that treatment with INH is associated
with an increase in insulin antibody levels,"
said Dr. Fineberg. "However, the analyses
done so far suggest that insulin antibodies are
not associated with increased HbA1c, insulin doses,
hypoglycemia rates, or allergic reactions. This
conclusion agrees with many other studies that
also show no apparent connection between insulin
antibodies and measurements of metabolic control
or clinical safety."
[Study
title: Inhaled Antibody Binding in Clinical Studies
of Inhaled Insulin (Exubera™ ) in Patients
with Type 1 or Type 2 Diabetes. Abstract 69]
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