by Peter J. Nebergall, Ph.D.
Not so long ago, if you used insulin, you didn't have a whole lot of choices. There was "normal" speed R insulin, slower NPH or Lente, and perhaps you considered using Ultralente. You used Lilly insulins, or those from Novo Nordisk. It was that way for decades.
No longer. Insulin innovations have come thick and fast. It is tough for us, and our doctors, to keep up. It seems every time we turn around there's not only a new oral diabetes medication, and a new theory about how diabetes works, but now also a new insulin. What's going on? What's on the way?
The biggest insulin changes of the last decade were two: First, the replacement of "animal-source" insulins (beef or pork) with recombinant-DNA types. The new types are cheaper, easier to produce, and, made in a test tube, do not attract the unwelcome attentions of groups like PETA.
The second change was the arrival of Eli Lilly's Humalog. Two to three times faster than R insulin, Humalog has enabled diabetics to "inject while looking at their food." Humalog starts quicker than R, peaks faster, and is gone from the body sooner. It has proved enormously popular.
Lilly's competitor, Novo Nordisk, has followed suit with Novolog, which, though different in formulation, is similar in pattern of action.
Another big change has been the arrival of Aventis' Lantus insulin. Much attention has been paid to "quick" insulins; but Lantus is a very slow insulin, with a "peak" so flat it's almost a straight line. The first "24-hour" insulin, Lantus is carving out a niche among type 2 diabetics who need to start injecting insulin. Lantus is chemically incompatible with other insulins, and cannot be mixed -- but, as one dose of Lantus lasts 24 hours, there would not be much occasion to mix it.
Lantus is not available in insulin pen cartridges at this time,
but sources at Novo Nordisk, who confirm the company is working on a competing
"slow" insulin, state: "Once our product is approved, we hope
to make it available for use in a variety of insulin delivery systems."
To achieve the best results, many people mix their insulins, injecting so many
units of a fast insulin plus so many units of a slower. This is generally done
in one syringe, by eye or with use of one of several assistive devices (see
"Blind Diabetics Can Draw Insulin Without Difficulty" in this issue).
Some people instead choose pre-mixed insulin, most often "70/30 (NPH and
R)," in vials and insulin pen cartridges.
Several new mixes are now available. Lilly offers a Humalog 75/25 (quick-acting
Humalog plus medium-slow PTZ insulin), and Novo Nordisk, maker of Novolin 70/30
premix, offers Novolog 70/30 premix. With their very rapid onset, these new
insulin premixes offer some real advantages; but the Novolog mix (reviewed elsewhere
in this issue) sounds dangerously like Novolin 70/30, opening the ambiguity
door to new possibilities for doctor and pharmacist error. If you expect Novolog
70/30, but receive the older Novolin 70/30, no big deal; you'll catch the error
next time you test your blood glucose -- but, if you expect Novolin 70/30, and
receive the Novolog mix, likely you're going down with a bang.
Amazingly, Novo Nordisk (who's sponsored really good research into insulin-dosage errors) did not sound particularly concerned, when I confronted them with this. I don't know why.
There has been a lot of interest in oral, buccal (under the
tongue), and inhalable insulins, whose administration would not require piercing
of the skin with a needle. Many companies are researching such formulations,
but none have been approved at this time. Insulin inhalation works (in that
the insulin gets into the bloodstream and lowers the blood sugar); but the problem
has always been to moderate the insulin's action, to give it a "response
curve" similar to that of injected insulin. Oral and buccal insulins, utilizing
the digestive system for absorption rather than the lungs, have had to contend
with the opposite: too little insulin getting through to the patient's blood.
There have been problems. One company's otherwise-promising clinicals revealed
that their inhalable insulin product did work -- but that it scarred the lungs
as well -- causing emphysema while controlling diabetes. Naturally, this formulation
did not pass its exam. Work continues, with the problem being "packaging"
of the insulin, in some sort of micro-droplets that can be absorbed in a reliable,
predictable, and controlled manner. And, of course, once a formulation works,
they'll have to prove it's safe -- and that will take some time.
An "insulin pill" is of course the ideal. This has been tried, many
a time, but the problem is simple: How do you keep the pill from digesting,
in the mouth and in the stomach, but get it to open up in the small intestine?
As with the inhalable formulations, there have been many different variations.
A lot of different companies are searching for this Holy Grail -- and with luck,
one of the experimental formulations will work. Eventually.
None of the inhalable insulins, or of the insulin pills, has completed clinical
trials at this time. There are a lot of trials underway -- but we're not there
yet.