Currently the only way insulin can be delivered is by injection. Inhaled insulin was available a few years ago, but was withdrawn from the market because of concerns of respiratory illness, and possible lung cancer due to the necessity of having high concentrations of insulin in the lungs to facilitate adequate absorption.
Oral insulins have been a dream of both patients and researchers for decades. But the technical aspects of preventing insulin from being digested by the enzymes in the gastrointestinal tract, along with the numerous barriers to absorption from the intestine, have been formidable.
Oral delivery of insulin has a number of potential advantages over current subcutaneous delivery. Psychologically and socially it is preferred by patients. Although pens and pumps have made taking insulin less burdensome, many people dislike taking mealtime insulin when they dine out. Compliance to medication regimens would likely increase if insulin could be given in pill form.
There are also a number of physiological benefits of oral insulin that mirror the benefits of endogenous insulin.
Insulin is normally secreted by the pancreatic beta cells and transported through the veins that drain the digestive system and pancreas. The insulin then makes it to the liver where approximately 80 percent is metabolized and bound to insulin receptors. This high concentration of insulin in the liver helps regulate and suppress excess hepatic glucose production, one of the hallmarks of type 2 diabetes.
Getting insulin into this circulation through injection isn’t very efficient, because of the quantity of insulin needed to achieve this effect. The large amounts of insulin required often causes more insulin in the system than is necessary to deal with glucose, which can lead to hypoglycemia and lipogensis (fat formation).The accumulation of fat leads to weight gain, and patients starting insulin therapy often experience an increase in weight. Some of this is caused by calories that used to be wasted in the urine due to untreated diabetes that are now retained by the body, but a small amount may be due to the fat build up from excess injected insulin .
Oral insulin avoids some of these difficulties, because it enters the body through pathways similar to those used by endogenous insulin. This means less insulin is necessary to achieve similar blood glucose control.
At present there is no available oral insulin, but initial trials of an oral insulin known as NN1954 created by Novo Nordisk have been completed. These studies reviewed NN1954 safety profile, tolerability and effect on glucose levels. The drug uses a technique called GIPET developed by Merrion Pharmaceuticals which helps retard digestion and improves absorption rates. Phase I trials are only the tip of the iceberg for drugs to receive FDA clearance but this is an exciting beginning.