I can’t remember any time in my 30 year career as a physician that there have been more new diabetes drugs released for type 2 diabetes within such a short period of time. We used to have only a few to choose from…glipizide, glimepiride and glyburide, and metformin. Now we also have Januvia®, Onglyza®, Tradjenta®, Nesina®, Byetta®, Bydureon®, Victoza®, Tanzeum®, Trulicity®, Invokana®, Farxiga® and Jardiance®. (Cycloset®) is a new type 2 medication that works in the brain and has been used for pituitary tumors that make too much prolactin. The diabetes version of (Cycloset®) is fast-acting form of bromocriptine (Cycloset®) and results in lowering of A1C.
Not to mention, all the combination medicines (ones that combine two diabetes medicines into one pill) like Osemia®, Kazano®, Kombiglyze®, Xigduo XR®, Glyaxmbi®, Invokanamet®. There are more, but I think you get the idea. This is truly the first time that it is hard for me to keep up with the names of the new diabetes therapies.
Type 2 patients also have a new mini daily insulin pump called the V-Go. There are also four new prescription weight loss medications, I almost forgot, there is another combination medication called Juvisync®, but instead of combining two diabetes medicines, it combines one for diabetes with one for cholesterol.
As if the names were not exhausting enough, the drug companies keep sending their representatives to tell me about how their medication is the one that can best help my patients. Yet, do any of these new or old therapies address the underlying cause of diabetes that being “beta cell burnout”? NO.
I am officially experiencing diabetes therapy burnout because there are too many diabetes and not a single one restores beta cells to normal. Some of the new classes of drugs like DPP-4 inhibitors have four drugs to choose from, not to mention the combinations with DPP-4 agents, yet none produce new functional beta cells within the islet.
What makes it worse are the blank stares that I get when I ask, “I want to know what you have new for type 1 diabetes?” They usually have no response. There is one! The new inhaled insulin Afrezza®, which replaces mealtime insulin and is loaded into a neat little inhaler using 4 or 8 unit cartridges at a time.
Even if type 1 only makes up 10% of all diabetes, I don’t see that 10% of new drug development from large pharmaceutical companies going into type 1 diabetes. Let’s review. Insulin was first used in 1922. The first rapid-acting insulin was approved in 1997, and the first basal insulin in 2000, and the only other new medication for type 1 has been pramlintide (Symlin®), in 2005. Symlin® is the analog of amylin, the hormone which is co-secreted with insulin in equal amounts to insulin from the islet’s beta cells.
Symlin® has been shown to reduce A1C levels, diminish pre-prandial insulin requirements, blunt high and low glycemic excursions, and suppress postprandial glucagon levels, which reduces the liver’s release of glucose release My team was the first to describe that Symlin® reduces postmeal glucagon resulting in lower postmeal glucose levels and demonstrated that Symlin® reduces both high and low glucose excursions in type 1 patients on insulin pumps. Although Symlin® has no effect on lowering glucose and does not result in hypoglycemia in people without diabetes, those on insulin must carefully reduce their insulin levels downward to avoid hypoglycemia when Symlin® is added.
From my perspective, I see each of the new type 2 therapies as being a Band-Aid. Each lowers A1C to a degree, but none address the underlying problem of too few beta cells. When there are too few beta cells to the point that diabetes occurs, whether we are talking about type 1 or type 2, havoc is wreaked on the other 5 hormones secreted by the islet.
In those of us lucky enough to not have diabetes, our islet hormones are in constant communication with each other, in order to maintain blood glucose levels below 125 mg/dL 95% of the time. When beta cell numbers are diminished, insulin and amylin are deficient. All five islet hormones other than insulin are required within a healthy islet to accomplish the great feat of normal glucose values.
Ghrelin is another hormone, which has been identified within the developing and adult islet and is produced by the islet’s epsilon cells. Abnormal ghrelin. Similar to ghrelin, impaired pancreatic polypeptide secretion from gamma cells within islets has been found in type 1 diabetes. Pancreatic polypeptide administration to type 1 patients on pumps has reduced insulin requirements and improved glucose metabolism.
Somatostatin, the 6th islet hormone, is from the delta cells and also fulfills multiple glucose regulatory roles. In studies among type 1 patients, somatostatin treatment has been associated with improvements in glucose metabolism.
Dr. Elliott Joslin knew that insulin was a diabetes treatment rather than a cure. To reverse diabetes requires more than insulin and even inhaled insulin, and more than all of the new pills, and injectables that we now have. New beta cells living inside healthy islets are what is necessary to maintain the function of the 6 islet hormones that communicate with each other all day long to maintain glucose levels below 125 mg/dL.
Perle is committed to restoring new islets with new beta cells and their neighboring alpha, gamma, delta, epsilon and pancreatic polypeptide cells. We are tackling beta cell burnout in type 1 first. That is our commitment.