What’s on the Horizon for Insulin?

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Researchers are developing more effective and efficient types of insulin, to make your care easier

With the massive and ever-expanding market for diabetes medications, the pharmaceutical companies are burning the midnight oil to outdo each other in the race to develop more perfect insulins and delivery systems.

We have come a long way, baby, but not nearly as far as we would like. The insulins we have today are certainly better than those of twenty years ago, but none would win an “endogenous insulin” look a-like contest.

Even with a pump, drug inception and degradation, timing, and consistency of results is far from ideal. Hyper- and hypoglycemia are ever present realities and the ability to eat a meal with significant amount of carbohydrate or fatty foods without doing intricate mathematical calculations about the precise time to give the injection is still a gleam in a researcher’s eye. And, of course, insulin made in the body comes with an injection free delivery system.

So what’s on the way?

Insulins with better timing

One type of product in development is ultra-rapid-acting insulin. These emerging insulins are aiming to more closely mimic the pattern of the body’s own first-phase insulin release. Depletion of first phase insulin response is highly correlated with the development of type 2 diabetes.

A bit of path physiology is in order here. For those without diabetes, prandial insulin is released in two phases: the first occurs as glucose concentrations rise from carbohydrate consumption, triggering a cascade of electrolyte activity in the beta cell. When calcium levels in the beta cells become sufficiently elevated, preformed insulin is secreted from storage granules in the cell.

This first-phase secretion is key to determining the body’s use of the incoming nutrient load; it directs the uptake of glucose by the body’s cells, suppresses the liver from making glucose and blunts postprandial glucose excursions. And the key point is that all of this happens really fast. First-phase secretion starts with 2 minutes of eating and continues for about 10 to 15 minutes.

The second phase involves the de novo synthesis of new insulin and continues through the digestive process for 2 to 3 hours. Insulin is not secreted continuously during this phase but rather oscillates on and off.

Patients with type 1 diabetes have little or no insulin response; people with type 2 have lost their first phase response.

What if you could take insulin orally? Or inhale it? Or even absorb it through your skin?

The goal for these ultra-rapids is to mimic as much as possible the speed of normal first phase insulin release. They will theoretically provide better coverage for food intake, suppress liver glucose output quicker and reduce the risk of hypoglycemia by leaving the body faster than the rapid insulins now on the market.

Insulins with longer coverage

Right now basal insulins last 24 hours, at the most. Sometimes people with type 1 have to take two injections of either Lantus® or Levemir® to maintain adequate control. But there are ultra-long-acting basal insulins in late stage development.

Instead of taking basal insulin once or twice a day, these insulins would allow you to take them three to four times a week. Researchers were able to achieve this longevity by altering the way the injected insulin dissolves into active insulin. (When insulin is injected into the fat tissue it is in the form of a hexamer- it needs to dissociate into a single molecule form to work properly.)

Delivery Methods

Part of the reason people are often distressed when told they have to go on insulin is that they have to inject it. Getting a flu shot once a year is no problem for most people; every day, several times a day for the rest of your life is tedious, no matter how painless the injections have become. Which is why, although it isn’t easy, the drug companies are pursuing oral, inhaled and transdermal alternate delivery systems.

To have an oral insulin work, it has to be encased in a protective type coating to allow it to escape digestion by our acidic gastric juices. This is a big problem, but progress is being made. The bet is that the obstacles won’t be insurmountable.

In addition to insulin by mouth, researchers are revisiting the possibility of inhaled insulin. And now instead of the mechanics of getting it into the lungs—that was worked out when it was previously on the market—late phase studies are concentrating on safety issues such as avoidance of late onset respiratory problems, and working out absorption profiles. (Exubera® was taken off the market in 2007 ostensibly due to lack of market share. However, there were reports of an increase in bronchial tumor rates in smokers who used the drug.)

If you can’t breathe it swallow it, perhaps you can absorb it through the skin. The patches under development are akin to nitroglycerin patches for people with heart disease, except they have an energy source to power ultrasonic wave transmission that would pulse the insulin through the skin pores.

It seems like there is a lot to look forward to: What modifications in insulin or insulin delivery would you like to see?

10 Responses to What’s on the Horizon for Insulin?

  1. thanks for the update – I’d love to hear more about “smart insulin”
    i.e. injectable insulin that only becomes active when glucose levels rise.

    -Eric Korenman

    • Sarah Gilbert says:

      I’m with Eric. As a mother with 2 boys 6 and 8 I am hopeful that Smart Insulin will be around in time fo them to go off to college! I listend to the man that invented it speak a few years back and he is amazing and so is the inulin!

  2. Jean Haight says:

    This is so utterly amazing!I have been on insulin since I was 18 mos old! There is a note in my chart at the Joslin Diabetes Center by the Original Dr Joslin!
    I am a walking history of diabetes! My father was in the Navy serving during the Korean War.my mother contacted Senator John F Kennedy who wrote numerous letters to have him be sent home with an honorable discharge!
    I was initially admitted to the Chelsea Naval Hospital!

    I’m not 100% certain of all the details from that point on!

    It is suspected that my Mothers,Fathers Mother probably had diabetes! At that time no one knew anything about Diabetes and they lived in Poland! My grandfather would carry her outside and place her in a chair to get some sun & Fresh Air!
    They didn’t even have insulin back then!
    I think the results that have come out of the Joslin Clinic and the next Generation of Insulin Products are going to be outstanding!
    I’m looking forward to this new insulin that you may be able to take by mouth!

  3. Jean Haight says:

    I’m willing to take part in any studies dealing with taking Insulin po! WOW!

    Thank God ! for the Drs at the Joslin and all the gifts that they have introduced for diabetics!

  4. I like the idea of smart insulin but what I would like to see more then anything new on the insulin horizon is a generic insulin that people can afford.

  5. RAY WARD says:

    i have been type 1 diabetic for 60 yrs. i am 76 years old ,take 4 shots a day 3 Humalog and 1 Lantus, i check my sugar 8 to 10 times day an night ,Ray Ward

    l

  6. Rose Kennedy says:

    Wow! I’m impressed with the Joslin’s continual striving for better diabetes treatments, as has been the case for the 52 year duration of my T1. For young people with diabetes, you have a future of good health and life. If I have made it thus far relatively unscathed, just imagine the what you can achieve, thanks to the tireless efforts and research of the Joslin Diabetes Center! Can you tell I’m a fan?!

  7. Erica Smyth says:

    Great easy to understand update. I have been using insulin for 38 years and research keeps making my life easier.

  8. amit jalan says:

    my son nikunj is 8 yrs now and is diabetic since he was 5.I wish science to find way that ensures better stability of glucose levels and make life of such persons easier.

  9. amit jalan says:

    My son nikunj is 8 yrs now and is diabetic since he was 5 .I wish science to find way that ensures better stability of glucose levels and make life of such persons easier.

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