New Treatments on the Way for Diabetes—Part 2

JANUARY 01, 2005
Amy Brian, PharmD, CGP, CPP

Traditionally, insulin has been available only as a more-thanonce- daily subcutaneous injection for patients. Insulin glargine (Lantus) is a synthetic insulin developed that simulates 24-hour basal insulin production, allowing certain patients with type 2 diabetes to reduce their insulin injections to just 1 a day. It has now become commonplace to treat patients with a combination of insulin and 1 or more oral hypoglycemic agents. Many patients, however, still search for a needleless alternative and are willing to take a combination of up to 3 oral hypoglycemic medications to avoid the needle stick involved with insulin administration. The development of inhaled insulin may help increase patient acceptability of necessary insulin treatment.

At the annual meeting of the American Diabetes Association, several preliminary studies on inhaled insulin were presented. Exubera is a fine, dry-powder, rapid-acting insulin that is under development. Some studies indicate that it may be at least as effective as injected insulin and may be superior to combination oral therapy for diabetes. One study included 470 patients who had type 2 diabetes that was uncontrolled on metformin therapy alone. Two groups were randomized to receive either adjunctive inhaled insulin or glyburide. Among patients with a baseline hemoglobin A1C (HgA1C) reading of >9.5%, those in the inhaled-insulin group demonstrated a 2.9% reduction in HgA1C, compared with a 2.5% reduction experienced by the glyburide group. The decline in HgA1C in patients with a baseline reading of <9.5% was similar in the 2 treatment groups.

Other summaries of phase 3 Exubera studies were presented as well. In one 52-week study, a group of 336 patients were treated with adjunctive inhaled insulin, and a second group of 291 patients were treated with combination oral therapy only. Decreases from baseline HgA1C were similar in the 2 groups, with an average decrease to 7.6% and 7.8% in the combination-inhaled-insulin group versus the combination-oral-therapy group, respectively. Episodes of hypoglycemia were similar in both treatment groups. Measured forced expiratory volume in 1 second was lowered to a greater extent in the Exubera group at both 24 and 52 weeks. The clinical significance of this finding is not known at this time. Additional safety testing is ongoing to determine whether any long-term compromise of pulmonary function or damage to lung tissue will be of concern.

The presence of insulin antibodies was noted to a greater extent in one study in patients using inhaled insulin versus traditional injected insulin. Although glycemic responses did not vary significantly between the groups, the clinical impact of insulin antibody production is not yet completely known.

Concern has been raised over the impact of cigarette smoking and the associated variability in inhaledinsulin absorption. A small study was presented that compared insulin action at 4 different time periods: during smoking and 90 minutes, 10 hours, and 4 weeks after the last cigarette was smoked. Patients were divided into those who were using nicotine- replacement products and those who were not. Overall, extreme variability in insulin action was reported in all groups—leading to the conclusion that inhaled insulin would not be appropriate for use by smokers or by patients using nicotine-replacement products.

Administration of insulin via the inhalation route would allow for preprandial insulin administration in both type 1 and type 2 diabetics. Potential advantages include better compliance in patients who are not willing to inject multiple daily insulin doses and glycemic control at least equivalent, if not superior, to that with conventional therapies. Several issues are still of concern, however. These issues include the possible link between inhaled insulin and adverse pulmonary effects, insulin antibody formation, and variability of absorption in smokers and in those with pulmonary disease. The promise of inhaled insulin is indeed an exciting new treatment option for persons with diabetes, but, until pulmonary safety concerns can be relieved, insulin injections will remain the most effective and only method available to deliver insulin.

Dr. Brian is a clinical specialist with Cornerstone Health Care, High Point, NC.