Alternate Insulin Deliverers.
Also known as the 'Insulin delivery wish list' or 'hopes for the future'.
Diabetes is a lucrative market. It is a disease that affects millions of people world wide and is spreading at a monumental rate. That means it is worthwhile to put a lot of money and time into research to develop the 'better mousetrap'.
Anyone who comes up with a better way of delivering insulin without pain and with minimal fuss and cost is going to be set up for life.
Various ideas have been, and are being, researched and developed and I will discuss these here.
Insulin patches.
We all know about nicotine patches that are used to help smokers give up their beloved cigarettes so you may be wondering why it is taking so long to produce a commercially available insulin patch.
The problem is the difference in the size of the molecules. Nicotine is a small molecule and passes easily through the pores of the skin. Insulin, on the other hand, is a large molecule and needs something to help get it through.
Researchers have been working on using ultrasound, electrical currents or chemicals to supply that help.
Different companies are using different techniques.
Starbridge Systems of Swansea, UK, won National Lottery funding in 2004 towards the development of their patch.
How it is going to work is best explained by the company itself, so below is a quote from the website of the Guardian:-
"Joseph Cefai, the co-founder and chief executive of Starbridge Systems, explained that the firm was developing tiny pumps able to respond to high-density light bursts.
The system involves the wax in the pumps melting and pushing drugs through tiny needles.
The laser-started pumps will be held in disposable "plasters" measuring about 10cm by 5cm (4in by 2in). These plasters will be controlled by small panels programmed by the patients, to allow doses to be varied according to blood-sugar levels.
Mr Cefai believes the patch will be able to carry up to three days' supply of insulin and will be easy to remove and stick to various parts of the body."
Dermisonics Inc. is producing a patch that uses ultrasonic waves to help force the insulin through. Known as the U-Strip (TM) Insulin Patch drug-delivery system this has got to the stage where trials are about to begin early in 2006. It has been targeted for type 2 diabetics.
For more information on this patch see DiabeticsInControl.com
Helix BioPharma Corp. has a patch that succeeded in reducing blood sugars in diabetic rats but research into the development of this patch for humans has yet to be announced.
It seems we must wait a while before our local pharmacy starts stocking any of the above. It is back to the old tried and tested ways for now.
Inhaled insulin.
This involves the use of either dry or dissolved insulin which is converted into tiny particles, usually by the use of compressed air, and then inhaled through the mouth, rather like one would if using an asthma inhaler.
The insulin passes directly into the lungs from where it is absorbed into the bloodstream.
There are already a number of inhalers out there which in trials have shown success in controlling Bg levels, but they are awaiting FDA approval. So far they all use rapid acting insulin so will not totally replace injections but may be of use as before meal boluses, for type 2 diabetics or for emergency situations. Research into the use of slow acting insulins is still underway.
Why, if they work, are they not yet available?
Well like most diabetic treatments they are not without their disadvantages.
1. This is a very wasteful method because only a small amount of the insulin inhaled actually reaches the bloodstream - figures quoted are 8-12%. Most of it lands up being deposited in the pharynx. One is going to need to use a lot to get the right amount to control your BG levels. Needless to say this is going to make this method rather costly. Figures quoted are around $4 -$4.50 a day as opposed to the 85c - $1 for standard insulin, assuming the use of said insulin 4 times a day.
2. Then there is the worry about the effect this will have on the lungs in the long term. Though lungs do have this wonderful surface area that seems custom made for this purpose in reality lungs were designed to deal with air, not insulin. What will happen to them after years and years of inhaled insulin?
Unfortunately early studies of inhaled insulin showed scarring and fibrosis in the lungs. Since then there have been improvements in the formulation of the insulin and changes to the inhalers and present studies show no major problems.
Still, this is one of the main concerns that is delaying the approval for general use.
3. Respiratory conditions such as colds or asthma reduce the absorption rate of the insulin.
4. Smokers also absorb inhaled insulin at a different rate to non-smokers.
5. There have been studies showing an increase in cholesterol levels with inhaled insulin.
Varieties of inhaled insulin.
Exubera is an inhaled short-acting insulin that is among the most advanced of all the inhaled insulins. A combined development by Sanofi-Aventis, Pfizer and Nektar Therapeutics (which developed the dry, powdered form of insulin and the inhaler) it has been filed for regulatory approval (for non-smokers only) in both the US and Europe. Pfizer must have faith in it getting passed because they have bought the sole rights to this drug from Sanofi-Aventis for $1.3 billion.
It has taken so long to get approval because a short-term decrease in lung function showed up during trials. This appears to stabilise eventually but is still an issue.
The actual inhaler is quite large, about the size of a small torch, but apparently the next generation one will be smaller.
New Development! Go to Exubera page.
AIR Insulin (human insulin inhalation powder; also known as HIIP).
This is the product of another collaboration, this time between Alkermes and Eli Lilly and Co. It is at present in Phase III trials.
So far it has not shown the effect on lung function that Exubera did.
The inhaler is small and sleek, about the size of a marker.
Technosphere Insulin System.
A product of the biopharmaceutical company Mannkind Corporation this is still in it's Phase 3 trial period. Consisting of a dry powder form of insulin developed by the company and a proprietary breath activated MedTone inhaler, this product claims to mimic the natural first-phase insulin release spike found in non-diabetics after the beginning of a meal. It also appears to work faster than the competitors.
It's delivery device is small, attractive (if you like purple) and easy to use.
They do not expect to file for FDA approval before 2008.
AERx
A product of yet another collaboration, this time between Novo Nordisk and Aradigm.
This system differs in that it is a battery powered device that uses liquid insulin, which has the disadvantage of needing refrigeration, unlike the dry powders.
However it has the advantage of being able to deliver minutely measured doses.
The Phase III clinical trial were put on hold because it was found that the drug was exiting the body to quickly. It was felt that the dosages needed to be re-examined and re-defined before trials could resume.
The deliverer is very large, about the same size as a paperback but does have the benefit of keeping a dosing log.
Another system undergoing research is that of delivering insulin in a nasal spray.
Bentley Pharmaceuticals, Inc in October, 2004 were doing phase 1 trials of such a intranasal insulin treatment
Buccal Insulin.
In a similar fashion to inhaled insulin this type of liquid insulin is delivered into the mouth where it is absorbed through the tongue, the inside of the cheeks and the lining of the back of the mouth and throat. It is even more wasteful of insulin than the inhaled version. However it does away with the problems of possible lung damage.
Having the honour to be named as the first commercialised non-injectable insulin product is the Canadian firm Generex Biotechnology's oral spray, brand named
Oral-Lyn (sometimes spelt Oralin).
However it's approval is solely from the Ecuadorian Ministry of Public Health, which it received in May 2005. Phase III clinical trials in the US and Europe still need to be carried out.
Insulin is delivered into the mouth via the companies own proprietary RapidMist device. It is designed to be used in the treatment of both type 1 and type 2 diabetes.
Insulin Pills.
As you already know it is not possible to take insulin in pill form because insulin is a protein and is broken down in the stomach, in the same way as the protein in your food, before it reaches the bloodstream where it could be used.
However knowing this has not stopped some few researchers from trying to find a way around it - seems they enjoy a challenge.
Some are trying to find ways of coating the pills in something that will circumvent the digestion process while others try to alter the structure of insulin to the same end.
The problem would again be one of wastage as well as the length of time before the pill started to work.
It is unlikely that pills will be available in the foreseeable future.
Pancreas transplantation.
This is usually done only when complications from diabetes, such as kidney damage, are so severe that there is no other choice.
No transplant is without it's inherent risks and this is no exception. However close the match between donor and recipient the body still sees the transplanted organ as foreign and attempts to destroy it. The recipient will have to be on anti-rejection drugs all their lives and some who have had the operation say that these are worse than having diabetes.
There is also the chance that the transplant will not 'take' and all the complicated surgery and trauma to the patient will have been in vain.
On the plus side, if the new pancreas is not rejected the patient will no longer need insulin as they will have a functioning pancreas producing it's own insulin and any diabetic complications that may have developed will be controlled or even sometimes healed.
However just getting a new pancreas does not do away with the auto-immune disease that caused the type 1 diabetes in the first place and it is possible that the new organ could be attacked in exactly the same way. It may buy you some insulin free time but at quite a cost.
Because of the lack of available cadaver pancreases it is possible to have a portion of a pancreas transplanted from a living relative.
Strangely enough the chance of rejection becomes less and that of survival greater if one has a kidney and pancreatic transplant at the same time. That is why pancreas transplants are nearly always done on people who have had or require a kidney transplant as well.
Islet cell transplants.
James Shapiro and Jonathan Lakey in Edmonton, Canada developed a procedure now known as the 'Edmonton Protocol'. This involved a immunosuppressive drug combination that was not toxic to islet cells, allowing for successful transplants.
The pancreas from a donor is subjected to a digestive enzyme, heat and shaking until the pancreas is dissolved and the islet cells are retrieved. They are then injected into the liver of the type 1 recipient, through a catheter inserted into a major blood vessel, the portal vein. Here they settle, gain a new blood supply and begin to produce insulin. The procedure does not require surgery but is technically difficult so requires specially trained staff. Also most patients need more than one transplant before producing enough insulin to stop their insulin injections.
As the cells in this case cannot be taken from a live donor (because of the possibility of destroying the pancreas) and it takes more than one donor pancreas to produce enough pure islet cells for the multiple injections required it is, shall we say, rather wasteful of pancreases.
If you are transplanting whole pancreases instead of islets the ratio is 1 pancreas to 1 recipient instead of a number of pancreases to 1 recipient. However it does allow one to use a pancreas that for some reason is unable to be used whole, so it can be said to better utilise the available resources.
Unfortunately the cost of this procedure is also very high, around $200,000, and is seldom covered by medical insurance.
It is normally reserved for those diabetics who have a very difficult time controlling their diabetes to the extent that it is interfering with their daily functioning - often called Brittle diabetics.
The fact that the recipient is going to have to take immunosuppression drugs for the rest of their lives really rules the procedure out for children, which is unfortunate.
For the latest results on the Edmonton trial and other developments go to our page on islet cell transplant.
Information on other research in this field can be found on
JDRF International 1
JDRF International 2