Are you a diabetic who is injecting insulin who would like some relief from daily shots? Or do you have family members who inject insulin but would rather not? This article might interest you.

The good news about insulin
Insulin is a hormone that is naturally produced in our body by the pancreas. Its main action is to regulate blood sugar by allowing sugar to enter the cells either for storage and later use, or to be used as an energy source. One of the major reasons for the high blood sugar in diabetes is insufficient release of insulin by the beta cells of the pancreas. A good strategy therefore to control high blood sugar among diabetics is to give insulin.

Insulin is the most effective anti-diabetic drug with unlimited capacity to lower blood sugar whose dose is limited only by its potential to also cause hypoglycemia or low blood sugar levels. It is efficient, causing blood sugar to go down within minutes to hours, and if used correctly can lead to good blood sugar control within hours to days. For patients who have type 1 diabetes, administration of insulin is absolutely essential to life. It is so vital that even skipping one dose could result in a life threatening complication called diabetic ketoacidosis or an abnormal accumulation of acid in the blood. As much as 30 percent of type 2 diabetics also need insulin for good control of their blood sugar as they may no longer respond adequately to their oral diabetic medications.

The problem with insulin
For some diabetic patients, daily insulin shots could sometimes make life difficult. Let’s face it, who likes to be pricked and poked? For kids and teens, it is not cool to be seen injecting insulin. For teens and adults, syringes always elicit suspicious glances from others who might think the diabetic to be a drug addict.

Insulin is a peptide or a protein-derived drug, and hence, cannot be taken by mouth, for it will be destroyed by the stomach acids, and will no longer work. It will therefore work best when given by injections, whether subcutaneously (directly pricking the skin with needles) or intravenously (through the veins).

Taking the ouch out
Progress in technology has allowed researchers to modify the way we administer insulin and therefore helped to improve the quality of life of patients who need to use insulin on a long term basis.The first few efforts to modify the way we use insulin is through the development of methods that improve the convenience, acceptability and ease of administration of the drug. Instead of syringes, insulin can be loaded into cartridges used with insulin pens. An insulin pen looks like a fountain pen and is usually slightly thicker in size. It has a disposable needle at one end with a cartridge that holds insulin and a dial that is used to select the insulin dose.

Insulin pens allow discreet injections since there is no need to carry a syringe and bottle of insulin. Doses can be conveniently dialed up, making dose errors less likely. Accurate dosing is possible even for those with limited vision who can listen to the clicks in the insulin dial, which count out the dose. For diabetic kids, some drug companies have made pens with various fancy designs that have made the insulin pen a cool device to use.

Some pens are disposable, while others are reusable, more environment-friendly with disposable glass cartridges that are replaced when consumed.

No shouts with the shorts
One of the major breakthroughs in technology for insulin users is the development of shorter and thinner monofilament needles. These needles have allowed insulin users to inject their dose by directly pricking the skin without the necessary “pinch” which thin individuals previously needed to do to avoid injecting the insulin into the muscle. Insulin when injected too deeply into the muscle tissue may lead to erratic blood sugar levels. Another advantage of the monofilament technology is to decrease the pain felt during injections; being a monofilament or developed from a single metal “wire”, this needle does not usually fray and catch on the skin leading to less pain.

From injection to inhalation
Over the years, various attempts have been made to make the use of insulin painless. Three alternative sites of delivery have been explored and have shown promise: into the lungs, into upper nasal pathways and through the stomach. Introduction of insulin though the lungs is the most promising route. Absorption into the bloodstream occurs through the thin walls of the lungs.

Several companies have tried to develop an inhaled form of insulin using various delivery systems. The U.S. FDA approved the first inhaled version of insulin called Exubera from Pfizer, Inc. in January 2006 and it became available for patient use soon after. This is approximately 84 years after the first insulin injections were given. However, by October 2007, Pfizer announced it would be dropping Exubera, citing that the drug had failed to gain the acceptance of patients and physicians. Despite being one of the most promising drugs, the use of inhaled insulin has several problems. The first major limitation common to all forms of inhaled insulin is the fact that this is a short-acting powder form of insulin that is used before each meal. To closely mimic our body’s natural insulin secretion, not only do we need short bursts during meals, but we also need the so-called basal insulin that is secreted moment to moment to closely regulate blood sugar. This means that all type 1 diabetic patients and some type 2 diabetics using inhaled insulin still need to inject long-acting insulin.

The second limitation is the large size of the device used for pulmonary drug administration. The Exubera inhaler is about the size of an eyeglass case when closed but opens to about 12 inches when used. This lack of discreet delivery was another issue repeatedly brought up by detractors of the device.

The third set of problems with the various forms of inhaled insulin is the reported side effects. They include coughing, shortness of breath, sore throat and dry mouth. It was also not approved for anyone with a lung disorder, such as asthma or chronic obstructive pulmonary diseases like emphysema because of some reversible decreases in lung function. Exercise also increases transport and likelihood of low blood sugar levels. Although many insulin users and doctors were disappointed with the withdrawal of this inhaled insulin other companies are continuing to develop other methods to deliver inhaled insulin.

The nose knows
Another painless way to deliver insulin is through the nose or the upper nasal airways. However, again there are several problems from this method foremost of which is the poor transport of insulin across the lining of the nasal passages. Delivery this way requires very large doses of insulin or use of a chemical to enhance insulin transport. These chemicals can however, often cause nasal irritation and a runny nose. Even a mild cold or stuffiness could easily change the intended insulin dose. About 1 00 units of insulin must be deposited into the nose to deliver 10 units into the blood. Insulin production costs would therefore seem prohibitive. This method is still currently still under investigation.

I am on the pill
Being on the pill used to mean that a woman was taking oral contraceptive pills. In the future, the phrase could mean being on the insulin pill. The best way to administer insulin (or any other drug for that matter) is orally or by mouth. This will allow diabetic patients to be more compliant as the drug would be easier to carry around, simpler and more discreet. Patients would be able to maintain privacy about their need to take insulin.

Many ideas are in the works from sprays to pills. The difficulty with insulin when taken orally is that digestive juices in the stomach and small intestines easily destroy the drug. Finding a coating for the pill that would protect it as it travels, and dissolves once it reaches the stomach is the initial problem. Also, the amount of insulin that can be put in a pill is small compared to what can be delivered in a syringe. There are now several researchers that are trying to find solutions to these problems with the insulin pill.

Recently, a novel drug delivery system, based on a unique liquid aerosol formulation, has been developed. Called OralinTM (oral insulin spray), this system allows precise insulin dose delivery via a simple metered dose inhaler. The system introduces fine-particle aerosolized droplets at high velocity into the patient’s mouth, with significant deposition of the drug and rapid absorption through the mucosal lining of the mouth and the pharynx. Like inhaled insulin it is short-acting and is able to control post-meal glucose rise in diabetic patients. This novel, pain-free, oral insulin formulation is rapidly absorbed, with a simple (user-friendly) administration technique, and precise dosing control comparable to injections. This method is still however undergoing human trials.

Other methods of administering insulin
One of the skin’s primary roles is to provide protection against infection and physical damage. This barrier is so effective that it prevents many drugs from crossing into the bloodstream. To overcome this defense, both passive and active drug transport across the skin (transdermal) barrier are being developed.

Passive transdermal delivery allows a drug to diffuse through the skin without pricking or disrupting it. These methods allow the drug to penetrate the small blood vessels and have an effect throughout the body (systemic effect). Passive delivery usually occurs with a patch, cream, or spray but only works with small molecule drugs, such as nicotine and aspirin. Insulin is far too large to get through the skin passively.

Active transdermal delivery, on the other hand, involves a chemical or mechanical disruption of the skin barrier. By using an applied force, such as ultrasound, high pressure (jet injectors) or a low voltage electrical current, active transdermal systems are capable of delivering proteins and other large molecule formulations through the skin and into the bloodstream. Again, these methods are still undergoing both animal and human experimentation.

Dreaming on….
At the moment, insulin is still best administered by injections. However, with the completion of human trials on these novel methods of giving drugs, we hope that soon we will be able to take the ouch out of insulin administration

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