Mannkind Corporation’s Afrezza has the potential to change the way diabetes is treated and could significantly reduce the complications and costs of diabetes.
Diabetes is now widely treated at an extremely high fasting glucose level of the order of around 170-220 mg/dl. This is done to counteract the extreme lows that follow today's insulin therapy so as to avoid serious hypo events. With rapid acting analogs (RAA’s) like Humalog & Novolog, the insulin takes 1 to 1.5 hours to peak and stays in the body for 5 to 7 hours. This is a reason people snack all day to avoid the hypos and they gain so much weight over time.
With current RAA's people need to calculate how many carbs they are going to eat even 30-60 minutes before they eat. That dictates the amount of insulin they need (this is called titration). Afrezza can lower the fasting level to around 100-110 mg/dl and maybe even lower with additional data. This is much closer to normal body function. Afrezza peaks in 12-14 minutes and exits the body within about three hours. With Afrezza, there are no huge lows so there is no need to snack all day. In addition with a normal meal, there is always no need for careful titration.
Afrezza mimics normal pancreatic early release and controls meal time glucose levels much better than RAA's or any other current therapy. It shuts down gluconeogenesis and some opinion leaders suggest that it may slow or even halt the progression of the disease.
Why do the FDA and prescribing doctors put so much value in HbA1c? HbA1c is approximately the average blood sugar level over about a three month period. It is recognized as a good measure of overall glucose control but it is not an independent measure of mealtime control alone. However, the FDA requires comparison testing of new drugs for non-inferiority in HbA1c to RAA's. The huge highs and the huge lows with the present insulins balance each other so the HbA1c for the present insulins for the most part seems good, when actually the huge swings are the crux of the problem with today's therapies. A huge high followed by a huge low is the major problem, not offsetting as the three month HbA1c would suggest.
There would be a huge advantage for an insulin that peaked in 10-20 minutes and leaves the body in just a couple hours that would mimic what is seen for a normal person without diabetes – without the highs and definitely with no huge lows.
Mannkind's Afrezza is a novel insulin that should replace RAA's so we can start eliminating the dangerous complications of diabetes. If the kinetics of this insulin therapy were better understood, this therapy would probably already have been approved.