Study Shows AFRESA(R) Provides Rapid Suppression Of Endogenous Glucose Production In Diabetes Patients

Main Category: Diabetes
Article Date: 30 Sep 2009 - 5:00 PDT

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AFRESA® (insulin human [rDNA origin]) Inhalation Powder is a well-tolerated, ultra rapid acting insulin able to more closely replicate normal glucose suppression than currently available insulins, according to data presented at the 45th Annual Meeting of the European Association for the Study of Diabetes. Results from the open-label, single-dose, three-way crossover study showed that endogenous glucose production (EGP) was suppressed earlier following AFRESA administration compared with subcutaneous insulin lispro and inhaled Exubera in adult patients with type 2 diabetes. The inability to effectively suppress endogenous glucose production significantly increases the risk of fasting hyperglycemia in individuals with type 2 diabetes.

"Many people do not appreciate that most of the excess postprandial glucose increase in individuals with diabetes is due to inadequate suppression of endogenous glucose production by the liver," said Jay S. Skyler, M.D., MACP, Professor, Division of Endocrinology, Diabetes, & Metabolism, Associate Director, Diabetes Research Institute, University of Miami Miller School of Medicine. "This study demonstrates that more rapid insulin availability better suppresses EGP."

AFRESA is a novel, ultra rapid acting mealtime insulin therapy with an action profile that mimics meal-related early insulin release. Based on an extensive phase 2/3 clinical program, a New Drug Application (NDA) is currently under review by the U.S. Food and Drug Administration (FDA) requesting approval to market AFRESA Inhalation Powder and the AFRESA Inhaler for use in adult patients with type 1 and type 2 diabetes mellitus for the treatment of hyperglycemia. AFRESA is conveniently administered by oral inhalation.

Study Design and Key Findings

Findings were based on endogenous glucose production (EGP) suppression in 18 insulin-treated subjects with type 2 diabetes mellitus and normal pulmonary function administered 45 U AFRESA administered by inhalation, 12 IU subcutaneous insulin lispro or 4 mg inhaled Exubera. The main study end-point was time to EGP suppression.

EGP suppression occurred earliest with AFRESA, followed by insulin lispro and Exubera (40, 75 and 130 minutes post-dose of the median EGP-time profiles, respectively). Significant differences between insulin lispro and Exubera were observed up to 40 minutes compared with AFRESA (p<0.002) and up to 2 hours for the Exubera-AFRESA comparison (p<0.05). Median total areas over the EGP curve were comparable across groups (1,938, 1,842 and 2,294 µmol/min). Median postprandial blood glucose areas under the curves were 53,343, 50,608 and 54,598 mg/dl•min for AFRESA, insulin lispro and Exubera, respectively.

About Diabetes

Diabetes, which affects 23.6 million people in the U.S., or 8 percent of the population, is characterized by the body's inability to properly regulate levels of blood glucose, or blood sugar. Insulin, a hormone produced by the pancreas, normally regulates the body's glucose levels, but in people with diabetes insufficient levels of insulin are produced (type 1 diabetes) or the body fails to respond adequately to the insulin it produces (type 2 diabetes). Current mealtime insulin therapy regimens have a number of limitations, including the risk of severe hypoglycemia, the likelihood of weight gain, inadequate post-meal glucose control, the need for complex titration of insulin doses in connection with meals and the need for injections. Additionally, current therapies do not mimic the natural time-action profile of insulin normally seen in healthy individuals and present challenges in maintaining compliance.

About Endogenous Glucose Production (EGP)

Glucose found in the bloodstream originates from both exogenous and endogenous sources. The primary source of "exogenous" glucose is ingested food, while "endogenous" glucose from the liver is a result of the breakdown of stored starches, and is supplied to the body during the fasted state. The high blood sugar that is associated with diabetes results from an imbalance between the absorption of glucose, systemic glucose production and glucose utilization. Suppression of Endogenous Glucose Production (EGP) is one of insulin's primary metabolic effects, and failure of this action is a major contributor to the high post-meal glucose concentrations associated with type 2 diabetes mellitus. It is thought that the loss of insulin spikes after a meal, characteristic of those patients with type 2 diabetes, resulting in insulin concentrations that are too low to suppress hepatic glucose production.

About AFRESA®

AFRESA® is a novel, ultra rapid acting mealtime insulin therapy being studied for use in adult patients with type 1 and type 2 diabetes mellitus for the treatment of hyperglycemia. It is a drug-device combination product, consisting of AFRESA Inhalation Powder pre-metered into single use dose cartridges and the light, discreet and easy to use AFRESA Inhaler. Administered at the start of a meal, AFRESA dissolves immediately upon inhalation and delivers insulin quickly to the blood stream. Peak insulin levels are achieved within 12 to 14 minutes of administration, effectively mimicking the release of meal-time insulin observed in healthy individuals. The AFRESA phase 2/3 clinical program included over 4,500 adult patients.

Source
MannKind Corporation

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