In individuals without diabetes, there is a normally occurring rapid and intense first phase insulin secretion in response to a meal. This spike is lost in patients with diabetes, who consequently experience higher and protracted blood glucose increases after a meal. Long-term uncontrolled elevations of blood glucose have been shown to cause irreversible damage.
Mannkind's study, reported at the ongoing American Diabetes Association annual meeting in San Diego, found that mimicking the first phase insulin release by giving a dose of its inhaled insulin preparation - TI - allowed glucose elimination to reach maximum levels much faster than with regular subcutaneous insulin.
Glucose elimination occurred in just 45 minutes with TI, compared to 240 minutes with subcutaneous insulin. It is important for patients with diabetes to have tight glucose control prior to, during and following a meal to avoid serious complications of diabetes like blindness and irreversible damage to the kidneys and nerves.
Meanwhile, a second study reported at the ADA found that this rapid onset of glucose control was not associated with any increase in hypoglycaemia, a serious complication that can follow insulin therapy.
Hypoglycaemia is a life-threatening situation where blood glucose falls below normal levels. It is a current therapeutic goal to bring blood glucose back to normal levels within 2-3 hours after a meal. However, conventional subcutaneous insulin doses that are sufficient to achieve this goal often extend their effect on glucose beyond the time when normal levels have been reached, potentially inducing hypoglycaemia late after a meal. The risk of hypoglycemia is an obstacle both for achieving good glucose control and reducing complications associated with diabetes.
In the ADA study, TI was found to exert about 74 per cent of its glucose lowering activity within the first three hours following administration. In contrast, regular subcutaneous insulin only exerted approximately 30 per cent of its activity within the same time period.
As a result, "TI appears to have the ability to achieve glucose lowering activity earlier than subcutaneous insulin without increasing the risk of late postprandial hypoglycaemia commonly associated with regular subcutaneous insulin,", said Mannkind.
TI is based on Mannkind's Technosphere drug delivery technology, which involves the inhalation of very small particles of the insulin formulation, using a proprietary inhaler device, that causes deposition of the active drug deep in the lungs.
A raft of companies are trying to bring non-injectable formulations of insulin to the multibillion dollar insulin market, with the first commercial launch of a product, Generex Biotechnology's Oral-Lyn, taking place in Ecuador last month. This formulation is delivered via an inhaler type device but is actually absorbed into the bloodstream through the buccal mucosa, with no lung deposition.
Meanwhile, Pfizer and Sanofi-Aventis filed for approval of their inhaled insulin product Exubera in the US in April, after delays caused by regulatory requests for data to support the safety of delivery the peptide into the lungs. Last September, the companies presented data suggesting that diabetics taking the drug exhibited no decline in lung function after two years. Other inhaled insulins are in Phase III clinical development from Eli Lilly/Alkermes and Novo Nordisk/Aradigm.