The availability of new agents for the treatment of type 2 diabetes, as well as new indications for existing agents, has broadened the therapeutic landscape for the disease, but without a map, the region can be difficult to navigate. To provide direction, the American College of Endocrinology and the American Association of Clinical Endocrinologists recently revised its “Road Maps for the Prevention and Treatment of Type 2 Diabetes.”

The three road maps—one each for treatment-naive patients, treated patients who had not reached the hemoglobin A_1c (HbA_1c) target, and patients at high risk for progression to diabetes—were introduced in 2005 to provide guidance for meeting existing diabetes treatment guidelines.

“We needed to update [them] because there have been a number of new products introduced, including inhaled insulin, basal insulin analogs, pramlintide, and DPP-4 inhibitors,” said Dr. Paul S. Jellinger, cochairman of the Road Map Task Force. “There are also new indications for some of the drugs already in use. For example, exenatide is now approved for use with [thiazolidinediones] in treatment-naive patients presenting with initial A_1c between 7%–8% who haven't achieved the target A_1c goal of 6.5% or lower with other therapies.”

Although other treatment algorithms have not yet included mention of the newer agents, “we've included recommendations on when and how to use them, based on A_1c-lowering data from FDA- [Food and Drug Administration]approved clinical trials and large randomized trials, as well as expert opinion,” said Dr. Jellinger, who is in private practice in Hollywood, Fla. “We want patients and clinicians to be able to take advantage of the newer-approved therapies without having to wait 10–20 years for more outcome data.”

The road maps also give physicians guidance and specificity all the way through the disease process, said Dr. Jaime A. Davidson, the other task force cochairman. “Rather than taking a treat-to-failure approach by waiting for patients to fail and then giving them a pill, the road maps use a treat-to-target approach from day 1, clearly indicating when to initiate therapy and with what agent. They also specify when to move on. For instance, instead of wasting a year to see if metformin by itself will get a given patient to target, the road maps define what agents to add if target is not met within 3 months.”

In addition, the road maps are geared to the needs of individual patients, continued Dr. Davidson, an endocrinologist at Medical City Dallas Hospital. “Rather than saying, 'We're going to start everyone who comes in with treatment-naive disease on metformin,' the road maps differentiate based on A_1c percentages. If someone comes in with an A_1c between 10%–11% and is symptomatic, they get insulin from day 1.”

That stratification is very important, Dr. Jellinger said. “Patients presenting with an A_1c between 10%–11% certainly require different treatment than those presenting at 7%–8%.” Although an HbA_1c greater than 10% is an indication for insulin in most patients, “other algorithms don't provide clear stratification, and many lump together everyone with an A_1c over 7%,” the glycemic target recommended by the American Diabetes Association.

As in the earlier road maps, the revised versions also advocate an “uncompromising treat-to-target” approach, in which the treatment targets are an HbA_1c value of 6.5% or less, fasting/preprandial glucose levels less than 110 mg/dL, and a 2-hour postprandial glucose level less than 140 mg/dL, as per guidelines from the American Association of Clinical Endocrinologists, said Dr. Jellinger. The goal “is to get patients to target as quickly as possible and to keep them there.”

The road maps help achieve this by targeting, in particular, the treatment of postprandial hyperglycemia in the lower HbA_1c ranges, which also distinguishes the resource from other algorithms. “Studies have shown that the postprandial glucose is higher in the lower A_1c ranges, while fasting hyperglycemia increases in the higher A_1c ranges,” said Dr. Jellinger. “This is why we recommend agents that affect postprandial control, such as the [meglitinide derivatives] and DPP-4 inhibitors, more prominently in treatment-naive patients in the lower A_1c range.”

To best meet and maintain AACE glycemic goals, therapeutic agents should be monitored and adjusted every 2–3 months. “If a treatment is not working as well as it should, change it. The road maps clearly tell you what to do, step by step, to meet and maintain the 6.5% A_1c goal,” said Dr. Jellinger.

In terms of prevention, the road maps stress early identification of high-risk individuals and describe lifestyle modifications and pharmacologic options that have been shown to stave off progression to type 2 diabetes. The document lists four glucose-lowering agents that have, in clinical studies, effectively delayed the onset of type 2 diabetes in high-risk patients, but the agents are not FDA-approved for prediabetes and, as such, AACE does not advocate their off-label use, Dr. Jellinger noted. “The drugs are listed because we recognize that physicians do use them to treat prediabetic individuals, particularly those with impaired glucose tolerance and multiple cardiovascular risk factors.” The AACE is currently developing a consensus conference on the treatment of prediabetes.

The revised road maps are available on the AACE Web site at www.aace.com/meetings/consensus/odimplementation/roadmap.pdf

'Road Maps' Chart Use of New Diabetes Drugs