Safety Confirmed for Inhaled Insulin in Interim Analysis

NEW YORK — The safety of inhaled insulin is holding up at 2 years in an ongoing study, with adverse pulmonary effects being small, occurring early, and proving reversible on cessation of the drug, Dr. Jay S. Skyler said at a meeting sponsored by the American Diabetes Association.

An interim analysis of a 51/2-year multinational study that includes 441 patients with type 1 diabetes has found that declines in pulmonary function—most likely age related—were similar among patients randomized to receive either subcutaneous or inhaled insulin (Exubera, Pfizer) plus basal insulin.

The mean changes in forced expiratory volume in 1 second at 3 months for inhaled and subcutaneous insulin were-0.047 and −0.026, respectively, and at 24 months the mean changes from baseline were −0.104 and −0.082. Only at the 3-month time point was the difference between the groups statistically significant, and concerns that changes in pulmonary function would progress—which would have been a real worry—have not been borne out, said Dr. Skyler, professor in the division of endocrinology, diabetes, and metabolism at the University of Miami, and the study's lead investigator.

There also have been concerns that repetitive inhalation of insulin particles could result in cumulative insults and the long-term development of fibrosis or tumors. “But the statistical likelihood of a few drops of powder or liquid hitting the same spot on a repetitive basis is trivial to nonexistent,” he said, noting that the surface area of the adult human lung approximates that of a tennis court.

Among the 217 patients receiving inhaled insulin who completed the first 2 years of the trial, there was a 33% reduction in risk of severe hypoglycemia compared with those receiving the drug subcutaneously (Diabetes Care 2007; 30:579–85).

Patients receiving inhaled insulin did develop antibodies at an increased rate, said Dr. Skyler. Mean insulin antibody levels at baseline were 4.50 and 4.15 mcU/mL in the inhaled and subcutaneous groups, respectively. At 2 years, the respective levels were 64.5 and 3.85 mcU/mL. “When a substance is taken in through the lung, the immune system reacts in a Th2 fashion, favoring antibody formation,” he said. However, the antibodies do not appear to interfere with efficacy or to be associated with adverse effects, he added.

Researchers also looked at efficacy in the interim analysis, and found that glycemic control was sustained and similar in both groups. Decreases in fasting glucose were greater in the inhaled insulin group, and weight gain was significantly less.

“If it works and doesn't appear to have any major problems, and is priced not very differently from other insulins, why has it done so poorly in the marketplace?” Dr. Skyler said.

Since Exubera was approved in January 2006, marketing efforts have focused specifically on endocrinologists. “I would submit that endocrinologists are the wrong target audience. We are not the ones who encounter the patients who are reluctant to use insulin,” he said.

“By the time patients reach us, with our team of nurse practitioners and educators, we can get people onto injected insulin with ease,” Dr. Skyler continued. Primary care physicians are more likely to see patients unwilling to go on injected insulin, and whether the use of inhaled insulin will increase when marketing efforts begin to target them remains to be seen, he said.

NEW YORK — The safety of inhaled insulin is holding up at 2 years in an ongoing study, with adverse pulmonary effects being small, occurring early, and proving reversible on cessation of the drug, Dr. Jay S. Skyler said at a meeting sponsored by the American Diabetes Association.

An interim analysis of a 51/2-year multinational study that includes 441 patients with type 1 diabetes has found that declines in pulmonary function—most likely age related—were similar among patients randomized to receive either subcutaneous or inhaled insulin (Exubera, Pfizer) plus basal insulin.

The mean changes in forced expiratory volume in 1 second at 3 months for inhaled and subcutaneous insulin were-0.047 and −0.026, respectively, and at 24 months the mean changes from baseline were −0.104 and −0.082. Only at the 3-month time point was the difference between the groups statistically significant, and concerns that changes in pulmonary function would progress—which would have been a real worry—have not been borne out, said Dr. Skyler, professor in the division of endocrinology, diabetes, and metabolism at the University of Miami, and the study's lead investigator.

There also have been concerns that repetitive inhalation of insulin particles could result in cumulative insults and the long-term development of fibrosis or tumors. “But the statistical likelihood of a few drops of powder or liquid hitting the same spot on a repetitive basis is trivial to nonexistent,” he said, noting that the surface area of the adult human lung approximates that of a tennis court.

Among the 217 patients receiving inhaled insulin who completed the first 2 years of the trial, there was a 33% reduction in risk of severe hypoglycemia compared with those receiving the drug subcutaneously (Diabetes Care 2007; 30:579–85).

Patients receiving inhaled insulin did develop antibodies at an increased rate, said Dr. Skyler. Mean insulin antibody levels at baseline were 4.50 and 4.15 mcU/mL in the inhaled and subcutaneous groups, respectively. At 2 years, the respective levels were 64.5 and 3.85 mcU/mL. “When a substance is taken in through the lung, the immune system reacts in a Th2 fashion, favoring antibody formation,” he said. However, the antibodies do not appear to interfere with efficacy or to be associated with adverse effects, he added.

Researchers also looked at efficacy in the interim analysis, and found that glycemic control was sustained and similar in both groups. Decreases in fasting glucose were greater in the inhaled insulin group, and weight gain was significantly less.

“If it works and doesn't appear to have any major problems, and is priced not very differently from other insulins, why has it done so poorly in the marketplace?” Dr. Skyler said.

Since Exubera was approved in January 2006, marketing efforts have focused specifically on endocrinologists. “I would submit that endocrinologists are the wrong target audience. We are not the ones who encounter the patients who are reluctant to use insulin,” he said.

“By the time patients reach us, with our team of nurse practitioners and educators, we can get people onto injected insulin with ease,” Dr. Skyler continued. Primary care physicians are more likely to see patients unwilling to go on injected insulin, and whether the use of inhaled insulin will increase when marketing efforts begin to target them remains to be seen, he said.

NEW YORK — The safety of inhaled insulin is holding up at 2 years in an ongoing study, with adverse pulmonary effects being small, occurring early, and proving reversible on cessation of the drug, Dr. Jay S. Skyler said at a meeting sponsored by the American Diabetes Association.

An interim analysis of a 51/2-year multinational study that includes 441 patients with type 1 diabetes has found that declines in pulmonary function—most likely age related—were similar among patients randomized to receive either subcutaneous or inhaled insulin (Exubera, Pfizer) plus basal insulin.

The mean changes in forced expiratory volume in 1 second at 3 months for inhaled and subcutaneous insulin were-0.047 and −0.026, respectively, and at 24 months the mean changes from baseline were −0.104 and −0.082. Only at the 3-month time point was the difference between the groups statistically significant, and concerns that changes in pulmonary function would progress—which would have been a real worry—have not been borne out, said Dr. Skyler, professor in the division of endocrinology, diabetes, and metabolism at the University of Miami, and the study's lead investigator.

There also have been concerns that repetitive inhalation of insulin particles could result in cumulative insults and the long-term development of fibrosis or tumors. “But the statistical likelihood of a few drops of powder or liquid hitting the same spot on a repetitive basis is trivial to nonexistent,” he said, noting that the surface area of the adult human lung approximates that of a tennis court.

Among the 217 patients receiving inhaled insulin who completed the first 2 years of the trial, there was a 33% reduction in risk of severe hypoglycemia compared with those receiving the drug subcutaneously (Diabetes Care 2007; 30:579–85).

Patients receiving inhaled insulin did develop antibodies at an increased rate, said Dr. Skyler. Mean insulin antibody levels at baseline were 4.50 and 4.15 mcU/mL in the inhaled and subcutaneous groups, respectively. At 2 years, the respective levels were 64.5 and 3.85 mcU/mL. “When a substance is taken in through the lung, the immune system reacts in a Th2 fashion, favoring antibody formation,” he said. However, the antibodies do not appear to interfere with efficacy or to be associated with adverse effects, he added.

Researchers also looked at efficacy in the interim analysis, and found that glycemic control was sustained and similar in both groups. Decreases in fasting glucose were greater in the inhaled insulin group, and weight gain was significantly less.

“If it works and doesn't appear to have any major problems, and is priced not very differently from other insulins, why has it done so poorly in the marketplace?” Dr. Skyler said.

Since Exubera was approved in January 2006, marketing efforts have focused specifically on endocrinologists. “I would submit that endocrinologists are the wrong target audience. We are not the ones who encounter the patients who are reluctant to use insulin,” he said.

“By the time patients reach us, with our team of nurse practitioners and educators, we can get people onto injected insulin with ease,” Dr. Skyler continued. Primary care physicians are more likely to see patients unwilling to go on injected insulin, and whether the use of inhaled insulin will increase when marketing efforts begin to target them remains to be seen, he said.