Reshuffling the Medication Choices for Type 2 Diabetes

Abstract & Commentary

By Joseph E. Scherger, MD, MPH, Clinical Professor, University of California, San Diego. Dr. Scherger reports no financial relationship to this field of study.

Synopsis: Leaders of the American Diabetes Association (ADA) joined with leaders of the European Association for the Study of Diabetes to reconsider the treatment strategy for patients with Type 2 diabetes. Insulin and sulfonylureas now join metformin as tier 1 medications. Tier 2 medications include the TZD pioglitazone (Actosä) and exenatide (Byetta®). Other medications should be used sparingly.

Source: Nathan DM, et al. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2008;31:1-11.

Until now the ADA in the United States and the Europeans have had different recommendations for the management of Type 2 diabetes. New medications have become available that have increased the options for treatment. To achieve a combined consensus and to provide affordable and effective therapy for the growing number of patients with type 2 diabetes, leaders of both organizations met to develop a consensus on new guidelines. The consensus statement published in the December 2008 issue of Diabetes Care precedes the expected publication of the revised formal guidelines in early 2009.

Five core types of diabetes medications are divided into two tiers with an algorithm for stepwise therapy. Tier 1 medications are metformin, sulfonylurea, and basal insulin, all considered the most effective and affordable. Tier 2 medications are pioglitazone and exenatide. Other medications such as acarbose (Precose®), repaglinide (Prandin®), sitagliptin (Januvia®), and pramlintide (Symlin®) are relegated to an "other" status and should be used only in "selected" patients.

The treatment algorithm has patients start lifestyle interventions and metformin at diagnosis. The recommended target of therapy is an A1C level of < 7%. The next step in therapy is to add basal insulin or a sulfonylurea. If control is not achieved, intensified insulin is recommended on top of the basal insulin injections. Combining insulin with a sulfonylurea is not recommended since they are not synergistic and the risk of hypoglycemia is increased.

If tier 2 is required or selected, pioglitazone or exenatide is added to lifestyle interventions and metformin. These tier 2 medications are not recommended with insulin. A sulfonylurea may be added to pioglitazone if needed. If control is not achieved with tier 2 medications, the physician should revert to lifestyle interventions, metformin, and insulin.


These authors from the United States and Europe are to be commended for staying with longstanding effective medications and not promoting newer and very expensive ones for a disease that is so common. What will happen if these recommendations become standard therapy (which they should)? More sulfonylurea will be used after metformin instead of a more expensive and less effective TZD. Many Type 2 diabetic patients resist the used of injections. There will also be more insulin used, a trend that has been growing for years. I am concerned that insulin use will drive up treatment costs because of the need for more frequent glucose testing by patients, an expense that can exceed the cost of the medications. This will be especially true for patients placed on intensified insulin therapy.

These new recommendations are only a minor change from the previous ADA guidelines that had a sulfonyl-urea, TZD, or basal insulin as choices after lifestyle change and metformin. Just the TZD, now only pioglitazone, has been removed as preferred choice. Rosiglitazone (Avandia®) is no longer recommended due to its heart disease risk.

These new guidelines will certainly not be the end of the story in treating Type 2 diabetes, even in the near future. This is an evolving area and new data emerge frequently. I see other combinations being recommended in the future, such as the use of exenatide with insulin. Once weekly exenatide is used commonly in Europe and, while its FDA approval has been delayed, it should be available in 2010.

Primary care physicians have the opportunity to stay on top of these treatment guidelines and be current in their care. I don't think the criticism is true anymore that primary care physicians adopt new changes after many years delay in this age of rapid exposure to new information.