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Administrating Insulin and Insulin Analogues

Inhaled Insulin

Introduction

An insulin inhaler

Photo from Nektar Therapeutics

Many people who are about to start on insulin injections inquire about alternatives to self injection. Insulin therapy has been around for eighty years, yet alternative methods of insulin delivery have been slow to emerge. The reason for this is that insulin is easily broken down by most methods tested and doesn’t really work that well. This page was written I response to the very many enquiries we receive with regard to alternative routes of insulin delivery.

What are the alternate routes of insulin delivery tested?

  • Oral – which requires the insulin to get past the stomach acid barrier
  • Buccal mucosa – absorption via the inner surface of the mouth
  • Nasal mucosa – absorption via the mucous membranes of the nose
  • Inhalers – where absorption occurs across the lung capillary bed

Why inhaled insulin?

We have used the inhaled route for delivery of drugs for several decades. The lungs offer a massive surface area where gas exchange occurs across the walls of terminal air spaces into the lung capillary bed.

Is it effective?

A recent study reported in ‘Diabetes Care’ compared the Aerodose inhaler with subcutaneous injected insulin. Patients received equivalent doses of inhaled insulin and subcutaneous insulin. Researchers found that the inhaled doses produced predictable and consistent insulin concentrations. The Aerodose inhaler is used to deliver aerosolised liquid insulin. There are other products which are undergoing similar studies.

Is it a substitute for all injected insulin?

No. It is very likely that the inhaled insulin will cover peaks in blood sugar after meals. Basal injection may still have to be injected.

What problems to developers face?

Delivering a drug by inhaler is not easy!

The main difficulty is the relatively large doses required which renders the technology expensive. In the study reported above inhaled doses of 80, 160 and 240 units were compared with much smaller amounts by injection, being 8, 16 and 24 units.

The particles produced by the inhalers would need to be small enough to reach the terminal air spaces in significant amounts.

Timing of doses is also an issue as the response to a dose may not be easy to predict.

The other theoretical concern is that insulin may act as a growth factor causing abnormalities and even cancer of the lung.

Is it available for use?

No. However these products are now in clinical trials and may be in general use within the next three years.

What are the different formulations in trial?

There are several systems in development by different pharmaceutical firms.

AerodoseR insulin inhaler uses an aerosol of liquid insulin (Aerogen Inc. CA USA). The Aerodose insulin inhaler is a small, hand-held device, (about the size of a cellular phone). The insulin cartridge holds enough insulin for approximately one week of dosing, for most patients, eliminating the inconvenience of carrying a separate insulin supply. 

ExuberaR – an inhaled, rapid-acting, dry-powder insulin, now in phase II clinical trials produced by Nektar Therapeutics (formerly Inhale Therapeutic Systems, Inc.), in partnership with Pfizer.

QdoseR inhaled insulin – (a joint venture between MicroDose Technologies, Inc. and Quadrant Drug Delivery Ltd., Nottingham) Currently in Phase I development.

A final word!

The prospect of needle-free insulin delivery remains an exciting concept for many people who face the daily task of self injection. It is unlikely that this will change substantially for many, given the high costs of developing new technology and bringing new drugs to the global market.

 

Dr Nishan Wijenaike
Consultant Diabetologist
West Suffolk Diabetes Service
November 2003