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New Major Changes in Recommendations for the Treatment of Type 2 Diabetes by ADA and EASD

Oct 28, 2008

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have issued an updated consensus statement on the management of hyperglycemia in patients with type 2 diabetes.

The updated statement, which focuses on the new classes of medications available to patients, is published conjointly in the October 22 Online First issue of Diabetes Care and the October 22 issue of Diabetologia. The article will also appear in the December print issue of Diabetes Care.

David M. Nathan, MD, from the Diabetes Center of Massachusetts General Hospital in Boston, and colleagues writes, "The epidemic of type 2 diabetes and the recognition that achieving specific glycemic goals can substantially reduce morbidity have made the effective treatment of hyperglycemia a top priority."  "While the management of hyperglycemia, the hallmark metabolic abnormality associated with type 2 diabetes, has historically taken center stage in the treatment of diabetes, therapies directed at other coincident features, such as dyslipidemia, hypertension, hypercoagulability, obesity, and insulin resistance, have also been a major focus of research and therapy.”

Maintaining glycemic levels as close to the nondiabetic range as possible has been demonstrated to have a powerful beneficial effect on diabetes-specific microvascular complications, including retinopathy, nephropathy, and neuropathy, in the setting of type 1 diabetes; in type 2 diabetes, more intensive treatment strategies have likewise been demonstrated to reduce microvascular complications."

The new statement updates a consensus algorithm for the medical management of type 2 diabetes published in August 2006. At that time, the authors recognized the need to update the algorithm based on the availability of new interventions and new evidence to validate their use, while recognizing the risks of changing the algorithm too often or without justification.
The principles used to develop the algorithm and its major features are still upheld in the latest revision. Although the January 2008 update to the consensus algorithm specifically addressed safety issues surrounding the thiazolidinediones, the current update highlights new classes of medications for which more clinical data and wider experience are now available.

"Selection of the individual agents should be made on the basis of their glucose-lowering effectiveness and other characteristics," the statement authors write. "However, when adding second antihyperglycemic medications, the synergy of particular combinations and other interactions should be considered. In general, antihyperglycemic drugs with different mechanisms of action will have the greatest synergy; insulin plus metformin is a particularly effective means of lowering glycemia while limiting weight gain."

Specific principles of management offered in the consensus statement are as follows:

  • An important therapeutic goal in type 2 diabetes is to achieve and to maintain near-normoglycemia (hemoglobin A1c level < 7.0%).
  • The initial treatment approach to type 2 diabetes should include lifestyle intervention and use of metformin.
  • When target glycemic goals are not achieved or maintained with the above first-line therapy, other medications should be added rapidly, and new regimens should be initiated.
  • In patients who do not reach target goals with the above regimens, early addition of insulin therapy should be considered.

Step 1 is lifestyle intervention and use of metformin because of its effect on glycemia, absence of weight gain or hypoglycemia, good tolerability profile, and relatively low cost. Lifestyle changes should aim to improve glucose levels, blood pressure, and lipid levels, and to promote weight loss or at least to avoid weight gain. As tolerated, metformin should be titrated to its maximally effective dose at 1 to 2 months.

Step 2 is to add another medication, either insulin or a sulfonylurea, within 2 to 3 months of starting step 1 or at any time when target hemoglobin A1c level is not achieved or if metformin is contraindicated or poorly tolerated. For patients who have hemoglobin A1c level of more than 8.5% or symptoms secondary to hyperglycemia, insulin is preferred, typically a basal (intermediate- or long-acting) insulin.

Step 3 involves further adjustments by starting or intensifying insulin therapy with additional injections that might include a short- or rapid-acting insulin given before selected meals to curtail postprandial hyperglycemia. Insulin secretagogues (sulfonylurea or glinides) should be discontinued, or tapered and then discontinued, once insulin injections are started.
The tier 2 algorithm consists of less well-validated therapies that may be considered in selected clinical settings, such as in patients with hazardous jobs that would make hypoglycemia particularly dangerous. In these patients, adding exenatide or pioglitazone may be considered, although rosiglitazone is not recommended.

For patients who need to lose weight and in whom hemoglobin A1c level is close to target (< 8.0%), exenatide may be considered. If these interventions do not achieve target hemoglobin A1c level or are not tolerated, adding a sulfonylurea may be helpful, or tier 2 interventions should be stopped and basal insulin started.

Although the amylin agonists, alpha-glucosidase inhibitors, glinides, and dipeptidyl peptidase 4 inhibitors are not included in the 2 tiers of preferred agents, they may be appropriate for selected patients. Compared with the first- and second-tier agents, their efficacy to lower glucose is less or equivalent, they are relatively expensive, and clinical data regarding their use are limited.

"Type 2 diabetes is epidemic," the statement authors conclude. "Its long-term consequences translate into enormous human suffering and economic costs; however, much of the morbidity associated with long-term microvascular and neuropathic complications can be substantially reduced by interventions that achieve glucose levels close to the nondiabetic range. Although new classes of medications and numerous combinations have been demonstrated to lower glycemia, current-day management has failed to achieve and maintain the glycemic levels most likely to provide optimal healthcare status for people with diabetes."

Practice Pearls

  • In type 2 diabetes, an important therapeutic goal is to achieve and to maintain hemoglobin A1c levels less than 7.0%. For most patients, step 1 is lifestyle intervention and metformin. When this fails to achieve or maintain target glycemic goals, other medications should be added rapidly, and new regimens should be started. Step 2 is to add another medication, either insulin or a sulfonylurea. In step 3, insulin therapy is started or intensified.
  • The tier 2 algorithm using less well-validated therapies may be considered in selected patients. For those in whom hypoglycemia would be particularly dangerous, exenatide or pioglitazone may be added, but rosiglitazone is not recommended. Exenatide may be considered for patients who need to lose weight and in whom hemoglobin A1c level is close to target (< 8.0%),

Diabetes Care. 2008;31:1-11. Published online October 22, 2008. Diabetologia. Published online October 22, 2008.


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