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needle free insulin options - Afrezza

Afrezza vs RAAs (Afrezza Units & Insulin:Carb Ratios)

Afrezza Units & Insulin:Carb Ratios

Afrezza and Insulin to carb ratios from Matt Bendall on Vimeo.

This video explains why insulin:carb ratios don’t work with Afrezza, no matter how hard you try.

Afrezza works so differently to previous insulins, and yet there is nothing on the box explaining how or why. It works so differently that for a while I wondered if I had a bad batch.

This video explains why the labelling on the box is unhelpful and confusing. The units just can’t be compared, and it takes a while to work out that Afrezza has two independent effects.

The first phase begins immediately but it doesn’t lower blood glucose, instead it temporarily stops it rising. This effect seems to be responsible for all the weird and wonderful properties of Afrezza, the first phase does not happen with previous insulins.

The second phase, however, works like a small dose of injectable insulin. It lowers blood glucose, and takes longer to start working. This is the only phase of Humalog or Apidra.

Previous treatments work by flooding the body with an unnaturally high level of insulin for hours, in order to slowly lower high blood glucose levels. Afrezza stops blood glucose rising in the first place using the natural first phase signal instead. This means that much lower, natural levels of insulin can now occur for the first time in T1 diabetics.

– Matt

You can also refer to this article on Afrezza’s activity curve, which points out that:

[a]ll the current injected insulins replace second phase insulin production. They take about an hour to start working and several more to exit the body. But Afrezza appears to replace first phase insulin production which just happens to be the part of insulin production that disappears first.  People diagnosed with Type 2 diabetes have usually lost all their first phase insulin production while retaining a lot of their second phase capability.  This means it might be an excellent drug for people recently diagnosed and one that is much safer than the drugs like Januvia or Victoza many are being put into at that time, whose dangers I have discussed elsewhere.”

Further, according to this article (Afrezza: Treating Diabetes in a Physiologic Manner):

“when a state of insufficient pancreatic insulin occurs, exogenous injected insulin products are available to replace the deficiency. THE PROBLEM is that current available products are not adequate, they are far from being able to replace the deficiency in a natural physiologic manner. The pharmacokinetic/dynamic profile of prandial (mealtime) insulins are much too slow, their activity does not become effective quickly enough and they persist far longer than is needed to control mealtime glucose. The current rapid acting insulin analogs (RAAs), which are the best of the current prandial products, do not reach a peak in the blood for close to an hour and persist for as long as 5-7 hours. To reasonably control the increase of glucose from the meal, the dose of such an insulin should be inconveniently injected about 15 or even 30 minutes before starting to eat. Of even greater concern, the slow activity produces a late excessive postprandial hyperinsulinemia which is the primary cause of dangerous hypoglycemia in today’s insulin therapy. That late persistence is one of the most significant problems with insulin therapy that clinicians and patients face today.

MannKind Corporation recognized the problems with current mealtime insulins and has developed a technology for drug stabilization. That technology was able to stabilize insulin monomers and the development was successful, creating a powder formulation called Technosphere Insulin that could effectively and efficiently be administered by oral inhalation that ELIMINATED subcutaneous prandial injections. This very rapid-acting insulin called Afrezza enters the blood very quickly, peaking in about 12-15 minutes and is eliminated from the body in a couple of hours. This pharmacokinetic/dynamic profile mimics what happens with insulin released in a person without diabetes and the result is significantly less hypoglycemia. It is even difficult to envision how there could be any hypoglycemia generated from properly timed Afrezza dosing. Much of the reduced level of hypoglycemia during the clinical trials was probably caused by the basal insulin or sulfonylureas (in type 2).

The Figure below shows the comparison between Afrezza and Bi-phasic Endogenous Insulin:

campbell-graphic-1

Although the dynamic response of Afrezza in the blood compares incredibly well to the total insulin response of a healthy person to an average short term meal, that is very different from the response of current prandial insulin products. The dynamic effects of the very-rapid-acting insulin and of the current prandial insulins are shown in the following Figure:

campbell-graphic-2

 

Current prandial insulins start far too slowly and last far too long. In my opinion, when one evaluates the pathophysiology of both type 1 and type 2 diabetes the pharmacokinetic/dynamic profile of Afrezza, an insulin that has now been approved by the FDA, it is seen that it creates an ideal profile to prevent the spikes in blood glucose levels after meals for both type 1 and type 2 patients. In type 2 patients, the first insulin problem is the loss of the first phase insulin release, so inhaling Afrezza should be a great treatment to overcome that physiologic defect in early type 2. For those with more advanced type 2, taking a basal insulin like Lantus or Levemir, adding Afrezza would greatly improve after meal elevations. For type 1 patients, a once daily shot of a basal insulin with inhalation of Afrezza for meals would much more likely simulate the normal physiologic release of insulin. Insulin pump patients could use Afrezza with each meal and take 1 shot of a basal insulin and greatly reduce the cost of treatment plus supplies. Afrezza does not cause a SHARPS problem and that is another major advantage. It could also be used for the many diabetes patients who have gastroparesis and those of us who have taken insulin over many years and have developed much scarring and thus unpredictable absorption of insulin. Also, Afrezza could be used by patients for correction doses when blood glucose levels are elevated. It is an especially good insulin for the many patients worldwide who detest insulin injections.”

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