ADA 2009: New Inhaled Insulin Has Rapid Onset of Action With No Adverse Effect on Lung Function

Martha Kerr

June 08, 2009

June 8, 2009 (New Orleans, Louisiana) — A new formulation of inhaled insulin called technosphere insulin (Afresa, Mannkind Corp) is safe and effective, with an onset of action similar to endogenous insulin. It has an extremely low incidence of hypoglycemia and is associated with some weight loss in patients with type 2 diabetes.

Importantly, the new formulation appears to have little adverse effect on pulmonary function, unlike its former competitor Exubera (Pfizer, taken off the market in October 2007).

Inhaled technosphere insulin is the subject of a large number of presentations here at the American Diabetes Association 69th Scientific Sessions.

Elizabeth Potocka, MD, clinical researcher at Mannkind Corporation in Valencia, California, and colleagues conducted a comparison of 45 U of inhaled technosphere insulin, 12 IU of subcutaneous lispro insulin (Humalog, Eli Lilly), and 4 mg of inhaled Exubera insulin with a meal challenge in 18 insulin-treated patients with type 2 diabetes and normal pulmonary function.

Swift Mechanism of Action

Technosphere insulin had an onset of action that was evident within 10 minutes of administration, compared with 30 to 40 minutes with both lispro and inhaled Exubera, Dr. Potocka told meeting attendees.

Peak trough in blood glucose was approximately 1.0 mmol/kg per minute with technosphere insulin at 40 minutes, compared with just over 2.0 mmol/kg per minute at approximately 70 minutes with lispro and 2.0 mmol/kg per minute at 2 hours with Exubera.

"Significant differences between lispro and Exubera were observed for up to 40 minutes, compared with technosphere insulin (P < .002), and up to 2 hours for the Exubera–technosphere insulin comparison (P < .05)," Dr. Potocka and colleagues write in their abstract.

"Endogenous glucose production was suppressed earlier following [technosphere insulin] administration, compared with subcutaneous insulin lispro and inhaled Exubera, which suggests that treatment with [technosphere insulin] may result in a more physiologic endogenous glucose production suppression," they conclude.

Comparable Efficacy, Less Weight Gain

A separate comparison of inhaled technosphere insulin with a rapid-acting analog (lispro), both given in combination with a long-acting analog (glargine, Lantus, Sanofi-Aventis), showed that Afresa plus glargine resulted in "comparable A1c reductions, more favorable 1-hour postprandial glucose levels, significantly less weight gain, and significantly less risk of hypoglycemia," Richard M. Bergenstal, MD, executive director of the International Diabetes Center in Minneapolis, Minnesota, told Medscape Diabetes & Endocrinology.

In a 52-week study, patients with type 1 diabetes and hemoglobin A1c values of 7% or greater were randomized to inhaled insulin with meals plus glargine (293 patients) or to glargine plus lispro (272 patients).

A1c reductions were similar in both groups, with a drop of 0.17% (±1.09) with inhaled insulin plus glargine and a drop of 0.47% (± 0.91) with glargine plus lispro (P = 0.38).

Fasting plasma glucose levels were significantly lower with glargine plus insulin (–44.9 ± 04.7) than with glargine plus lispro (–23.4 ± 0.3; P = .0052).

One-hour postprandial glucose levels were 165.7 mg/dL (±8.2 mg/dL) with inhaled insulin plus glargine and 201.7 mg/dL (±82.3 mg/dL) with glargine plus lispro (P = .0022).

The inhaled insulin group lost weight (0.5 ± 0.1 kg), whereas the glargine plus lispro group gained weight (1.4 ± 3.9 kg), with a statistically significant difference (P < .0001).

Finally, the inhaled insulin plus glargine group had a statistically significant reduction in the incidence of mild-to-moderate hypoglycemia, compared with glargine plus lispro (odds ratio [OR], 0.474; confidence interval [CI], 0.0271 - 0.831; P = .0091), and total episodes of hypoglycemia (OR, 0.488; CI, 0.278 - 0.856; P = .0124).

No Adverse Effect on Pulmonary Function

Technosphere insulin appears to have no adverse effect on pulmonary function compared with Exubera, John Gerich, MD, professor of medicine at the University of Rochester School of Medicine in New York, told Medscape Diabetes & Endocrinology in an interview during the meeting.

Dr. Gerich was commenting on results presented by Nikhil Amin, MD, of Mannkind Corporation, who reported data on forced expiratory volume in 1 second (FEV1), forced vital capacity, total lung capacity, and carbon monoxide diffusion test over a 2-year period in 730 patients with type 1 or 2 diabetes on inhaled insulin, 824 patients on usual oral antidiabetic medications, and 145 healthy controls on no specific therapy.

Pulmonary function tests declined equally in all 3 groups over the 2-year period, including the nondiabetics, Dr. Amin told meeting attendees.

"There was no difference in mean change in FEV1 from baseline to 24 months between inhaled insulin and usual care," he said.

"This drug comes up clean in safety testing, which was a concern with Exubera," Dr. Gerich said. "In addition, it showed noninferiority with conventional diabetic therapy."

"The absence of hypoglycemia and the lack of weight gain were significant findings. There was even a suggestion of weight loss with [inhaled insulin]," Dr. Gerich added. "Afresa has a profile that is very similar to the body's own insulin production in response to meals. The kinetics are about the same as in people without insulin."

"Patients tend to prefer a once-a-day pill, in my experience. They don't want to have to take something every time they eat unless they have to," Dr. Gerich commented. "But this is easy to deliver, with a device that is the very similar to a regular inhaler, for coverage with meals for patients who need that."

These studies were supported by Mannkind Corporation. Dr. Gerich disclosed receiving some financial support from Mannkind Corporation, but he was not directly involved with these studies.

American Diabetes Association (ADA) 69th Scientific Sessions: Abstract 232-OR, presented June 6, 2009; abstract 479-P, presented June 8, 2009; and abstract 570-P, presented June 7, 2009.