Array of therapeutic agents now available for diabetes treatment

Exciting developments coming in future.

Issue: August 2006

ByPhilip Levy, MD, FACE

Philip Levy, MD, FACE [photo]
Philip Levy

What a wonderful time it is for those of us who have the privilege of taking care of people with diabetes mellitus. Diabetes has been known for thousands of years, but the relationship of the pancreas and glucose first became known in the late 1800s. The development of injectable insulin in the year 1921 in Toronto by Banting and Best is a historical landmark in the history of diabetes. The development of antibiotics in the World War II years led us to the discovery that certain sulfa drugs could lower blood glucose.

When I first started in this field we had sulfonylureas and regular NPH and PZI insulin as well as the Lente insulins, which had just been developed. Blood glucose self-monitoring and HbA1c were not yet on the scene or even imagined. We were still testing urines for glucose and depended on the occasional plasma glucose as a monitor of control. The research emphasis was to develop a long-acting insulin that could be taken once a day. Insulin injections in those days were difficult and painful, and needles had to be used over and over again.

The development of blood glucose self-monitoring and the ability to measure HbA1c marked a significant advance for the patients with diabetes, since they were now able to take some degree of control over diabetes and became a very active part of the equation of care. The concept of a diabetes health care team was developed, leading to the certification of diabetes educators, who have assumed a vital role in the care of diabetes.

In the early 1990s in the United States, we still had the same medications that had been available for many years. Metformin was used in other countries but was late getting released in the U.S. We therefore had better methods of following people with diabetes, but did not have the necessary pharmaceuticals to ensure better control. Insulin pumps had come along, but they were primitive, as were the insulins used in them. We thought that tight control would mean better outcomes, but we weren’t sure.

Then developments started to explode. The Diabetes Control and Complications Trial (DCCT) and later the United Kingdom Prospective Diabetes Study (UKPDS) were completed and showed that tight control really did make a difference in long-term outcomes. Analog insulins were coming onto the scene, and we now have three excellent rapid acting analogs: lispro, aspart and glulisine. We also have excellent long acting analogs: glargine and detemir. In addition, we have several premixes of analog insulin with rapid- and intermediate-acting mixtures.

This array of insulins has given us valuable tools for treatment and has allowed for better control in the setting of increased lifestyle flexibility. The rapid-acting insulins have also proved to be effective in insulin pump therapy, while the pumps themselves have become more and more sophisticated. Inhaled insulin has been approved by the FDA and should be available by the time this editorial is published.

We have also seen the development of new oral agent classes for the treatment of type 2 diabetes. None of these agents were introduced before the early 1990s. First metformin became available as a medication to decrease hepatic glucose production and increase insulin sensitivity. Then along came the thiazolidinediones, rosiglitazone and pioglitazone, which are potent in decreasing insulin resistance. In addition, PPAR alpha and gamma agonists have been studied and might play a role in our therapeutic armamentarium in the future. Shortly we are going to see the release of several dipeptyl peptidase iv inhibitors which will inhibit the breakdown of GLP-1. Endocannabinoid receptor inhibitors are under study and may play a significant role in amelioration of the metabolic syndrome, which is so intimately associated with type 2 diabetes. Many of these agents have been combined for use as combination therapy treating insulin resistance and beta-cell deficiency.

In addition to the oral agents, there are several injectables which were recently released and can be used in type 2 diabetes. Exenatide, a GLP-1 analog, became available recently and has been widely used. Pramlintide, an amylin analogue, has also been marketed for use in type 1 and type 2 diabetes.

What an array of therapeutic agents we now have at our disposal! And what is yet to come? This issue of Endocrine Today is dedicated to type 2 diabetes. We are privileged today to have so many therapeutic tools available, and we look forward to new exciting developments in the future.

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Philip Levy, MD, FACE, is a Clinical Professor of Medicine at the University of Arizona College of Medicine, a practicing clinician at the Phoenix Endocrinology Clinic and a member of Endocrine Today’s Editorial Advisory Board.