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Type 2 Diabetes Drugs
A Growing Number of Options

by Joshua J. Neumiller, PharmD, CDE, CGP, FASCP, and Sally To, PharmD

In recent years, the number of medicines approved to treat Type 2 diabetes has grown at an amazing rate. Metformin, which is often the diabetes drug of first choice today, came on the market in the United States in 1994. At that time, metformin, insulin, and a class of drugs known as sulfonylureas were the only medicines available to treat Type 2 diabetes. Today, in contrast, there are 11 classes of drugs on the market for Type 2 diabetes, with even more expected to appear in the not-too-distant future. While it is reassuring to have so many options available, trying to understand how all of these drugs work — and the pros and cons of each — can be a bit overwhelming. To help you get a handle on this, this article briefly reviews all drugs currently approved in the United States for the treatment of Type 2 diabetes.

Basics of Type 2 diabetes
Before delving into the topic of drugs and how they work to lower blood glucose, it helps to understand what happens in Type 2 diabetes that leads to elevated blood glucose levels.

While ongoing research is always expanding our knowledge of what happens in Type 2 diabetes, the condition is known to stem from three related but distinct problems: insulin resistance, reduced insulin production, and overproduction of glucose by the liver.

The pancreases of people with Type 2 diabetes often produce insulin just fine, but a hallmark of the condition is that their bodies cannot use the hormone efficiently. This resistance to the effects of insulin, aptly known as insulin resistance, makes it more difficult for the body’s cells to “take up” glucose from the bloodstream and use it for energy — since insulin controls this process.

When a person is insulin resistant, the pancreas is forced to produce more insulin to maintain normal blood glucose levels. Over time, this stresses the pancreas until it cannot keep up with the insulin needs of the body. Eventually the pancreas may become “burned out” and lose its ability to make insulin altogether.

Finally, in people with Type 2 diabetes the liver tends to produce excess glucose, raising the blood glucose level inappropriately. Normally, the liver releases just enough glucose into the bloodstream to keep the body running smoothly. In the presence of insulin resistance, however, the signals telling the liver to stop releasing glucose don’t work, and it continues to release it even when blood glucose levels are too high.

Together, these three processes (and others that we are still learning about) lead to hyperglycemia, or high blood glucose.

ADA/EASD algorithm
While this article covers all drugs and therapies currently available to treat Type 2 diabetes, it is important to note that expert medical bodies recommend using some of these drugs before using others. The American Diabetes Association (ADA), along with the European Association for the Study of Diabetes (EASD), released the latest version of an algorithm in 2009 that recommends an order of treatment for Type 2 diabetes. An algorithm is a set of steps to follow to achieve a desired end; in this case, the desired end is a diabetes regimen that keeps blood glucose levels in target range.

Many health-care providers use this algorithm to guide their treatment decisions for people with Type 2 diabetes, starting with metformin and lifestyle changes at diagnosis and proceeding to other recommended therapies as needed. The algorithm groups treatments into Tier 1, “well-validated therapies”, and Tier 2, “less well-validated therapies.”

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